COVID-19-Associated Hospitalizations and Maternal Vaccination Among Infants Aged <6 Months - COVID-NET, 12 States, October 2022-April 2024.

Infants aged <6 months are at increased risk for severe COVID-19 disease but are not yet eligible for COVID-19 vaccination; these children depend upon transplacental transfer of maternal antibody, either from vaccination or infection, for protection. COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) data were analyzed to estimate COVID-19-associated hospitalization rates and identify demographic and clinical characteristics and maternal vaccination status of infants aged <6 months hospitalized with laboratory-confirmed COVID-19. During October 2022-April 2024, COVID-NET identified 1,470 COVID-19-associated hospitalizations among infants aged <6 months. COVID-19-associated hospitalization rates among young infants were higher than rates among any other age group, except adults aged ≥75 years, and are comparable to rates among adults aged 65-74 years. The percentage of hospitalized infants whose mothers had been vaccinated during pregnancy was 18% during October 2022-September 2023 and decreased to <5% during October 2023-April 2024. Severe outcomes among infants hospitalized with COVID-19 occurred frequently: excluding newborns hospitalized at birth, approximately one in five young infants hospitalized with COVID-19 required admission to an intensive care unit, nearly one in 20 required mechanical ventilation, and nine infants died during their COVID-19-associated hospitalization. To help protect pregnant persons and infants too young to be vaccinated, prevention for these groups should focus on ensuring that pregnant persons receive recommended COVID-19 vaccines.

COVID-19-Associated Hospitalizations Among U.S. Adults Aged ≥65 Years - COVID-NET, 13 States, January-August 2023.

Adults aged ≥65 years remain at elevated risk for severe COVID-19 disease and have higher COVID-19-associated hospitalization rates compared with those in younger age groups. Data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to estimate COVID-19-associated hospitalization rates during January-August 2023 and identify demographic and clinical characteristics of hospitalized patients aged ≥65 years during January-June 2023. Among adults aged ≥65 years, hospitalization rates more than doubled, from 6.8 per 100,000 during the week ending July 15 to 16.4 per 100,000 during the week ending August 26, 2023. Across all age groups, adults aged ≥65 years accounted for 62.9% (95% CI = 60.1%-65.7%) of COVID-19-associated hospitalizations, 61.3% (95% CI = 54.7%-67.6%) of intensive care unit admissions, and 87.9% (95% CI = 80.5%-93.2%) of in-hospital deaths associated with COVID-19 hospitalizations. Most hospitalized adults aged ≥65 years (90.3%; 95% CI = 87.2%-92.8%) had multiple underlying conditions, and fewer than one quarter (23.5%; 95% CI = 19.5%-27.7%) had received the recommended COVID-19 bivalent vaccine. Because adults aged ≥65 years remain at increased risk for COVID-19-associated hospitalization and severe outcomes, guidance for this age group should continue to focus on measures to prevent SARS-CoV-2 infection, encourage vaccination, and promote early treatment for persons who receive a positive SARS-CoV-2 test result to reduce their risk for severe COVID-19-associated outcomes.

Maternal negative affect moderates behavioral and physiological synchrony in Latinx and Black mother-child dyads.

Positive behavioral synchrony (PBS) between mothers and children involves the bidirectional exchange of verbal and nonverbal communication. Respiratory sinus arrhythmia (RSA) synchrony reflects the concordance between mother-child physiological states. Both PBS and RSA synchrony can be undermined by psychopathology symptoms. Latinx and Black families may experience contextual stressors that contribute to heightened symptoms of psychopathology, yet minimal research has examined relations between psychopathology symptoms with PBS and RSA synchrony in these families. The present study assessed associations between maternal depressive and child internalizing symptoms, mother and child negative affect (NA), and PBS and RSA synchrony in a sample of 100 Latina and Black mothers (Mage  = 34.48 years, SD = 6.39 years) and their children (Mage  = 6.83 years, SD = 1.50 years). Dyads engaged in a video-recorded stress task where RSA was collected continuously. Videos were later coded for PBS and mother and child NA. Mothers reported on their depressive and child's internalizing symptoms. Maternal NA was associated with weak PBS and negative RSA synchrony. Neither depressive and internalizing symptoms nor child NA were associated with PBS or RSA synchrony. Results highlight the potency of maternal NA on behavioral and physiological synchrony in Latinx and Black families.

Complications in children with ventricular assist devices: systematic review and meta-analyses.

Heart failure is a significant cause of mortality in children with cardiovascular diseases. Treatment of heart failure depends on patients' symptoms, age, and severity of their condition, with heart transplantation required when other treatments are unsuccessful. However, due to lack of fitting donor organs, many patients are left untreated, or their transplant is delayed. In these patients, ventricular assist devices (VADs) are used to bridge to heart transplant. However, VAD support presents various complications in patients. The aim of this study was to compile, review, and analyse the studies reporting risk factors and aetiologies of complications of VAD support in children. Random effect risk ratios (RR) with 95% confidence intervals were calculated to analyse relative risk of thrombosis (RR = 3.53 [1.04, 12.06] I2 = 0% P = 0.04), neurological problems (RR = 0.95 [0.29, 3.15] I2 = 53% P = 0.93), infection (RR = 0.31 [0.05, 2.03] I2 = 86% P = 0.22), bleeding (RR = 2.57 [0.76, 8.66] I2 = 0% P = 0.13), and mortality (RR = 2.20 [1.36, 3.55] I2 = 0% P = 0.001) under pulsatile-flow and continuous-flow VAD support, relative risk of mortality (RR = 0.45 [0.15, 1.37] I2 = 36% P = 0.16) under left VAD and biVAD support, relative risk of thrombosis (RR = 1.72 [0.46, 6.44] I2 = 0% P = 0.42), infection (RR = 1.77 [0.10, 32.24] I2 = 46% P = 0.70) and mortality (RR = 0.92 [0.14, 6.28] I2 = 45% P = 0.93) in children with body surface area < 1.2 m2 and > 1.2 m2 under VAD support, relative risk of mortality in children supported with VAD and diagnosed with cardiomyopathy and congenital heart diseases (RR = 1.31 [0.10, 16.61] I2 = 73% P = 0.84), and cardiomyopathy and myocarditis (RR = 0.91 [0.13, 6.24] I2 = 58% P = 0.92). Meta-analyses results show that further research is necessary to reduce complications under VAD support.

Laboratory-Confirmed COVID-19-Associated Hospitalizations Among Adults During SARS-CoV-2 Omicron BA.2 Variant Predominance - COVID-19-Associated Hospitalization Surveillance Network, 14 States, June 20, 2021-May 31, 2022.

Beginning the week of March 20­26, 2022, the Omicron BA.2 variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating variant in the United States, accounting for >50% of sequenced isolates.* Data from the COVID-19­Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to describe recent COVID-19­associated hospitalization rates among adults aged ≥18 years during the period coinciding with BA.2 predominance (BA.2 period [Omicron BA.2 and BA.2.12.1; March 20­May 31, 2022]). Weekly hospitalization rates (hospitalizations per 100,000 population) among adults aged ≥65 years increased threefold, from 6.9 (week ending April 2, 2022) to 27.6 (week ending May 28, 2022); hospitalization rates in adults aged 18­49 and 50­64 years both increased 1.7-fold during the same time interval. Hospitalization rates among unvaccinated adults were 3.4 times as high as those among vaccinated adults. Among hospitalized nonpregnant patients in this same period, 39.1% had received a primary vaccination series and 1 booster or additional dose; 5.0% had received a primary series and ≥2 boosters or additional doses. All adults should stay up to date† with COVID-19 vaccination, and multiple nonpharmaceutical and medical prevention measures should be used to protect those at high risk for severe COVID-19 illness, irrespective of vaccination status§ (1).Beginning the week of March 20­26, 2022, the Omicron BA.2 variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating variant in the United States, accounting for >50% of sequenced isolates.* Data from the COVID-19­Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to describe recent COVID-19­associated hospitalization rates among adults aged ≥18 years during the period coinciding with BA.2 predominance (BA.2 period [Omicron BA.2 and BA.2.12.1; March 20­May 31, 2022]). Weekly hospitalization rates (hospitalizations per 100,000 population) among adults aged ≥65 years increased threefold, from 6.9 (week ending April 2, 2022) to 27.6 (week ending May 28, 2022); hospitalization rates in adults aged 18­49 and 50­64 years both increased 1.7-fold during the same time interval. Hospitalization rates among unvaccinated adults were 3.4 times as high as those among vaccinated adults. Among hospitalized nonpregnant patients in this same period, 39.1% had received a primary vaccination series and 1 booster or additional dose; 5.0% had received a primary series and ≥2 boosters or additional doses. All adults should stay up to date† with COVID-19 vaccination, and multiple nonpharmaceutical and medical prevention measures should be used to protect those at high risk for severe COVID-19 illness, irrespective of vaccination status§ (1).

Hospitalizations of Children and Adolescents with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, July 2021-January 2022.

The first U.S. case of COVID-19 attributed to the Omicron variant of SARS-CoV-2 (the virus that causes COVID-19) was reported on December 1, 2021 (1), and by the week ending December 25, 2021, Omicron was the predominant circulating variant in the United States.* Although COVID-19-associated hospitalizations are more frequent among adults,† COVID-19 can lead to severe outcomes in children and adolescents (2). This report analyzes data from the Coronavirus Disease 19-Associated Hospitalization Surveillance Network (COVID-NET)§ to describe COVID-19-associated hospitalizations among U.S. children (aged 0-11 years) and adolescents (aged 12-17 years) during periods of Delta (July 1-December 18, 2021) and Omicron (December 19, 2021-January 22, 2022) predominance. During the Delta- and Omicron-predominant periods, rates of weekly COVID-19-associated hospitalizations per 100,000 children and adolescents peaked during the weeks ending September 11, 2021, and January 8, 2022, respectively. The Omicron variant peak (7.1 per 100,000) was four times that of the Delta variant peak (1.8), with the largest increase observed among children aged 0-4 years.¶ During December 2021, the monthly hospitalization rate among unvaccinated adolescents aged 12-17 years (23.5) was six times that among fully vaccinated adolescents (3.8). Strategies to prevent COVID-19 among children and adolescents, including vaccination of eligible persons, are critical.*.

Hospitalization of Adolescents Aged 12-17 Years with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, March 1, 2020-April 24, 2021.

Most COVID-19-associated hospitalizations occur in older adults, but severe disease that requires hospitalization occurs in all age groups, including adolescents aged 12-17 years (1). On May 10, 2021, the Food and Drug Administration expanded the Emergency Use Authorization for Pfizer-BioNTech COVID-19 vaccine to include persons aged 12-15 years, and CDC's Advisory Committee on Immunization Practices recommended it for this age group on May 12, 2021.* Before that time, COVID-19 vaccines had been available only to persons aged ≥16 years. Understanding and describing the epidemiology of COVID-19-associated hospitalizations in adolescents and comparing it with adolescent hospitalizations associated with other vaccine-preventable respiratory viruses, such as influenza, offers evidence of the benefits of expanding the recommended age range for vaccination and provides a baseline and context from which to assess vaccination impact. Using the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), CDC examined COVID-19-associated hospitalizations among adolescents aged 12-17 years, including demographic and clinical characteristics of adolescents admitted during January 1-March 31, 2021, and hospitalization rates (hospitalizations per 100,000 persons) among adolescents during March 1, 2020-April 24, 2021. Among 204 adolescents who were likely hospitalized primarily for COVID-19 during January 1-March 31, 2021, 31.4% were admitted to an intensive care unit (ICU), and 4.9% required invasive mechanical ventilation; there were no associated deaths. During March 1, 2020-April 24, 2021, weekly adolescent hospitalization rates peaked at 2.1 per 100,000 in early January 2021, declined to 0.6 in mid-March, and then rose to 1.3 in April. Cumulative COVID-19-associated hospitalization rates during October 1, 2020-April 24, 2021, were 2.5-3.0 times higher than were influenza-associated hospitalization rates from three recent influenza seasons (2017-18, 2018-19, and 2019-20) obtained from the Influenza Hospitalization Surveillance Network (FluSurv-NET). Recent increased COVID-19-associated hospitalization rates in March and April 2021 and the potential for severe disease in adolescents reinforce the importance of continued COVID-19 prevention measures, including vaccination and correct and consistent wearing of masks by persons not yet fully vaccinated or when required by laws, rules, or regulations.†.

Showcasing Nursing Leadership and Contributions to a University's COVID-19 Student Contact Tracing Process.

The COVID-19 pandemic was an unprecedented event that impacted every segment of healthcare, including universities preparing healthcare professionals. Instituting processes to coordinate student return to campus and ongoing COVID-19 testing and contract tracing challenged university campuses, but also brought opportunities for collaboration. This article reports on the experiences of one nonprofit private higher education university in management of the COVID-19 testing and contact tracing that were led by school of nursing faculty and nursing leadership.

Disparities in COVID-19 Incidence, Hospitalizations, and Testing, by Area-Level Deprivation - Utah, March 3-July 9, 2020.

Coronavirus disease 2019 (COVID-19) has had a substantial impact on racial and ethnic minority populations and essential workers in the United States, but the role of geographic social and economic inequities (i.e., deprivation) in these disparities has not been examined (1,2). As of July 9, 2020, Utah had reported 27,356 confirmed COVID-19 cases. To better understand how area-level deprivation might reinforce ethnic, racial, and workplace-based COVID-19 inequities (3), the Utah Department of Health (UDOH) analyzed confirmed cases of infection with SARS-CoV-2 (the virus that causes COVID-19), COVID-19 hospitalizations, and SARS-CoV-2 testing rates in relation to deprivation as measured by Utah's Health Improvement Index (HII) (4). Age-weighted odds ratios (weighted ORs) were calculated by weighting rates for four age groups (≤24, 25-44, 45-64, and ≥65 years) to a 2000 U.S. Census age-standardized population. Odds of infection increased with level of deprivation and were two times greater in high-deprivation areas (weighted OR = 2.08; 95% confidence interval [CI] = 1.99-2.17) and three times greater (weighted OR = 3.11; 95% CI = 2.98-3.24) in very high-deprivation areas, compared with those in very low-deprivation areas. Odds of hospitalization and testing also increased with deprivation, but to a lesser extent. Local jurisdictions should use measures of deprivation and other social determinants of health to enhance transmission reduction strategies (e.g., increasing availability and accessibility of SARS-CoV-2 testing and distributing prevention guidance) to areas with greatest need. These strategies might include increasing availability and accessibility of SARS-CoV-2 testing, contact tracing, isolation options, preventive care, disease management, and prevention guidance to facilities (e.g., clinics, community centers, and businesses) in areas with high levels of deprivation.

Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States, March 1-30, 2020.

Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)† to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources.

Characteristics and Maternal and Birth Outcomes of Hospitalized Pregnant Women with Laboratory-Confirmed COVID-19 - COVID-NET, 13 States, March 1-August 22, 2020.

Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19) (1,2). The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) (3) collects data on hospitalized pregnant women with laboratory-confirmed SARS-CoV-2, the virus that causes COVID-19; to date, such data have been limited. During March 1-August 22, 2020, approximately one in four hospitalized women aged 15-49 years with COVID-19 was pregnant. Among 598 hospitalized pregnant women with COVID-19, 54.5% were asymptomatic at admission. Among 272 pregnant women with COVID-19 who were symptomatic at hospital admission, 16.2% were admitted to an intensive care unit (ICU), and 8.5% required invasive mechanical ventilation. During COVID-19-associated hospitalizations, 448 of 458 (97.8%) completed pregnancies resulted in a live birth and 10 (2.2%) resulted in a pregnancy loss. Testing policies based on the presence of symptoms might miss COVID-19 infections during pregnancy. Surveillance of pregnant women with COVID-19, including those with asymptomatic infections, is important to understand the short- and long-term consequences of COVID-19 for mothers and newborns. Identifying COVID-19 in women during birth hospitalizations is important to guide preventive measures to protect pregnant women, parents, newborns, other patients, and hospital personnel. Pregnant women and health care providers should be made aware of the potential risks for severe COVID-19 illness, adverse pregnancy outcomes, and ways to prevent infection.

In vivo reprogramming of non-mammary cells to an epithelial cell fate is independent of amphiregulin signaling.

Amphiregulin (AREG)-/- mice demonstrate impaired mammary development and form only rudimentary ductal epithelial trees; however, AREG-/- glands are still capable of undergoing alveologenesis and lactogenesis during pregnancy. Transplantation of AREG-/- mammary epithelial cells into cleared mouse mammary fat pads results in a diminished capacity for epithelial growth (∼15%) as compared to that of wild-type mammary epithelial cells. To determine whether estrogen receptor α (ERα, also known as ESR1) and/or AREG signaling were necessary for non-mammary cell redirection, we inoculated either ERα-/- or AREG-/- mammary cells with non-mammary progenitor cells (WAP-Cre/Rosa26LacZ+ male testicular cells or GFP-positive embryonic neuronal stem cells). ERα-/- cells possessed a limited ability to grow or reprogram non-mammary cells in transplanted mammary fat pads. AREG-/- mammary cells were capable of redirecting both types of non-mammary cell populations to mammary phenotypes in regenerating mammary outgrowths. Transplantation of fragments from AREG-reprogrammed chimeric outgrowths resulted in secondary outgrowths in six out of ten fat pads, demonstrating the self-renewing capacity of the redirected non-mammary cells to contribute new progeny to chimeric outgrowths. Nestin was detected at the leading edges of developing alveoli, suggesting that its expression may be essential for lobular expansion.

Intersection of the p63 and NF-κB pathways in epithelial homeostasis and disease.

Overexpression of ΔNp63α, a member of the p53/p63/p73 family of transcription factors, is a molecular attribute of human squamous cancers of the head and neck, lung and skin. The TP63 gene plays important roles in epidermal morphogenesis and homeostasis, regulating diverse biological processes including epidermal fate decisions and keratinocyte proliferation and survival. When overexpressed experimentally in primary mouse keratinocytes, ΔNp63α maintains a basal cell phenotype including the loss of normal calcium-mediated growth arrest, at least in part through the activation and enhanced nuclear accumulation of the c-rel subunit of NF-κB (Nuclear Factor-kappa B). Initially identified for its role in the immune system and hematopoietic cancers, c-Rel has increasingly been associated with solid tumors and other pathologies. ΔNp63α and c-Rel have been shown to be associated in the nuclei of ΔNp63α overexpressing human squamous carcinoma cells. Together, these transcription factors cooperate in the transcription of genes regulating intrinsic keratinocyte functions, as well as the elaboration of factors that influence the tumor microenvironment (TME). This review provides an overview of the roles of ΔNp63α and c-Rel in normal epidermal homeostasis and elaborates on how these pathways may intersect in pathological conditions such as cancer and the associated TME.

Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis.

The p63 gene is a member of the p53/p63/p73 family of transcription factors and plays a critical role in development and homeostasis of squamous epithelium. p63 is transcribed as multiple isoforms; ΔNp63α, the predominant p63 isoform in stratified squamous epithelium, is localized to the basal cells and is overexpressed in squamous cell cancers of multiple organ sites, including skin, head and neck, and lung. Further, p63 is considered a stem cell marker, and within the epidermis, ΔNp63α directs lineage commitment. ΔNp63α has been implicated in numerous processes of skin biology that impact normal epidermal homeostasis and can contribute to squamous cancer pathogenesis by supporting proliferation and survival with roles in blocking terminal differentiation, apoptosis, and senescence, and influencing adhesion and migration. ΔNp63α overexpression may also influence the tissue microenvironment through remodeling of the extracellular matrix and vasculature, as well as by enhancing cytokine and chemokine secretion to recruit pro-inflammatory infiltrate. This review focuses on the role of ΔNp63α in normal epidermal biology and how dysregulation can contribute to cutaneous squamous cancer development, drawing from knowledge also gained by squamous cancers from other organ sites that share p63 overexpression as a defining feature.

Influenza Vaccination Modifies Disease Severity Among Community-dwelling Adults Hospitalized With Influenza.

Background: We investigated the effect of influenza vaccination on disease severity in adults hospitalized with laboratory-confirmed influenza during 2013-14, a season in which vaccine viruses were antigenically similar to those circulating. Methods: We analyzed data from the 2013-14 influenza season and used propensity score matching to account for the probability of vaccination within age strata (18-49, 50-64, and ≥65 years). Death, intensive care unit (ICU) admission, and hospital and ICU lengths of stay (LOS) were outcome measures for severity. Multivariable logistic regression and competing risk models were used to compare disease severity between vaccinated and unvaccinated patients, adjusting for timing of antiviral treatment and time from illness onset to hospitalization. Results: Influenza vaccination was associated with a reduction in the odds of in-hospital death among patients aged 18-49 years (adjusted odds ratios [aOR] = 0.21; 95% confidence interval [CI], 0.05 to 0.97), 50-64 years (aOR = 0.48; 95% CI, 0.24 to 0.97), and ≥65 years (aOR = 0.39; 95% CI, 0.17 to 0.66). Vaccination also reduced ICU admission among patients aged 18-49 years (aOR = 0.63; 95% CI, 0.42 to 0.93) and ≥65 years (aOR = 0.63; 95% CI, 0.48 to 0.81), and shortened ICU LOS among those 50-64 years (adjusted relative hazards [aRH] = 1.36; 95% CI, 1.06 to 1.74) and ≥65 years (aRH = 1.34; 95% CI, 1.06 to 1.73), and hospital LOS among 50-64 years (aRH = 1.13; 95% CI, 1.02 to 1.26) and ≥65 years (aRH = 1.24; 95% CI, 1.13 to 1.37). Conclusions: Influenza vaccination during 2013-14 influenza season attenuated adverse outcome among adults that were hospitalized with laboratory-confirmed influenza.

Hormone signaling requirements for the conversion of non-mammary mouse cells to mammary cell fate(s) in vivo.

Mammotropic hormones and growth factors play a very important role in mammary growth and differentiation. Here, hormones including Estrogen, Progesterone, Prolactin, their cognate receptors, and the growth factor Amphiregulin, are tested with respect to their roles in signaling non-mammary cells from the mouse to redirect to mammary epithelial cell fate(s). This was done in the context of glandular regeneration in pubertal athymic female mice. Our previous studies demonstrated that mammary stem cell niches are recapitulated during gland regeneration in vivo. During this process, cells of exogenous origin cooperate with mammary epithelial cells to form mammary stem cell niches and thus respond to normal developmental signals. In all cases tested with the possible exception of estrogen receptor alpha (ER-α), hormone signaling is dispensable for non-mammary cells to undertake mammary epithelial cell fate(s), proliferate, and contribute progeny to chimeric mammary outgrowths. Importantly, redirected non-mammary cell progeny, regardless of their source, have the ability to self-renew and contribute offspring to secondary mammary outgrowths derived from transplanted chimeric mammary fragments; thus suggesting that some of these cells are capable of mammary stem cell/progenitor functions.

Resting respiratory sinus arrythmia and cognitive reappraisal moderate the link between political climate stress and anxiety symptoms in Latina and Black mothers.

Guided by the Family Stress Model for minority families, the present study examined the potential buffering effect of resting respiratory sinus arrythmia (RRSA), cognitive reappraisal, and mindfulness on the association between political climate stress (PCS) and anxiety symptoms in a sample of Latina and Black mothers. Participants were 100 mothers living in the southeastern United States. Mothers reported on PCS, cognitive reappraisal, mindfulness, and symptoms of anxiety. RRSA were measured during a resting task. Moderation analyses tested the influence of these three factors (RRSA, cognitive reappraisal, mindfulness) on the relation between PCS and anxiety. Results showed that the relation between PCS and anxiety symptoms was strongest at low levels of RRSA and cognitive reappraisal. At high levels of these two factors, there was no association between PCS and anxiety symptoms. Mothers with high levels of RRSA and cognitive reappraisal may be able to interact with and evaluate environmental stimuli in such a way that allows for adaptive adjustment, buffering against the negative impact of PCS. RRSA and cognitive reappraisal may be important targets of interventions designed to address the rising rates of anxiety symptoms in Latina and Black mothers.

Laboratory-Confirmed Influenza-Associated Hospitalizations Among Children and Adults - Influenza Hospitalization Surveillance Network, United States, 2010-2023.

Problem/Condition: Seasonal influenza accounts for 9.3 million-41 million illnesses, 100,000-710,000 hospitalizations, and 4,900-51,000 deaths annually in the United States. Since 2003, the Influenza Hospitalization Surveillance Network (FluSurv-NET) has been conducting population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in the United States, including weekly rate estimations and descriptions of clinical characteristics and outcomes for hospitalized patients. However, a comprehensive summary of trends in hospitalization rates and clinical data collected from the surveillance platform has not been available. Reporting Period: 2010-11 through 2022-23 influenza seasons. Description of System: FluSurv-NET conducts population-based surveillance for laboratory-confirmed influenza-associated hospitalizations among children and adults. During the reporting period, the surveillance network included 13-16 participating sites each influenza season, with prespecified geographic catchment areas that covered 27 million-29 million persons and included an estimated 8.8%-9.5% of the U.S. population. A case was defined as a person residing in the catchment area within one of the participating states who had a positive influenza laboratory test result within 14 days before or at any time during their hospitalization. Each site abstracted case data from hospital medical records into a standardized case report form, with selected variables submitted to CDC on a weekly basis for rate estimations. Weekly and cumulative laboratory-confirmed influenza-associated hospitalization rates per 100,000 population were calculated for each season from 2010-11 through 2022-23 and stratified by patient age (0-4 years, 5-17 years, 18-49 years, 50-64 years, and ≥65 years), sex, race and ethnicity, influenza type, and influenza A subtype. During the 2020-21 season, only the overall influenza hospitalization rate was reported because case counts were insufficient to estimate stratified rates. Results: During the 2010-11 to 2022-23 influenza seasons, laboratory-confirmed influenza-associated hospitalization rates varied significantly across seasons. Before the COVID-19 pandemic, hospitalization rates per 100,000 population ranged from 8.7 (2011-12) to 102.9 (2017-18) and had consistent seasonality. After SARS-CoV-2 emerged, the hospitalization rate for 2020-21 was 0.8, and the rate did not return to recent prepandemic levels until 2022-23. Inconsistent seasonality also was observed during 2020-21 through 2022-23, with influenza activity being very low during 2020-21, extending later than usual during 2021-22, and occurring early during 2022-23. Molecular assays, particularly multiplex standard molecular assays, were the most common influenza test type in recent seasons, increasing from 12% during 2017-18 for both pediatric and adult cases to 43% and 55% during 2022-23 for pediatric and adult cases, respectively. During each season, adults aged ≥65 years consistently had the highest influenza-associated hospitalization rate across all age groups, followed in most seasons by children aged 0-4 years. Black or African American and American Indian or Alaska Native persons had the highest age-adjusted influenza-associated hospitalization rates across these seasons. Among patients hospitalized with influenza, the prevalence of at least one underlying medical condition increased with increasing age, ranging from 36.9% among children aged 0-4 years to 95.4% among adults aged ≥65 years. Consistently across each season, the most common underlying medical conditions among children and adolescents were asthma, neurologic disorders, and obesity. The most common underlying medical conditions among adults were hypertension, obesity, chronic metabolic disease, chronic lung disease, and cardiovascular disease. The proportion of FluSurv-NET patients with acute respiratory signs and symptoms at hospital admission decreased from 90.6% during 2018-19 to 83.2% during 2022-23. Although influenza antiviral use increased during the 2010-11 through the 2017-18 influenza seasons, it decreased from 90.2% during 2018-19 to 79.1% during 2022-23, particularly among children and adolescents. Admission to the intensive care unit, need for invasive mechanical ventilation, and in-hospital death ranged from 14.1% to 22.3%, 4.9% to 11.1%, and 2.2% to 3.5% of patients hospitalized with influenza, respectively, during the reported surveillance period. Interpretations: Influenza continues to cause severe morbidity and mortality, particularly in older adults, and disparities have persisted in racial and ethnic minority groups. Persons with underlying medical conditions represented a large proportion of patients hospitalized with influenza. Increased use of multiplex tests and other potential changes in facility-level influenza testing practices (e.g., influenza screening at all hospital admissions) could have implications for the detection of influenza infections among hospitalized patients. Antiviral use decreased in recent seasons, and explanations for the decrease should be further evaluated. Public Health Action: Continued robust influenza surveillance is critical to monitor progress in efforts to encourage antiviral treatment and improve clinical outcomes for persons hospitalized with influenza. In addition, robust influenza surveillance can potentially reduce disparities by informing efforts to increase access to preventive measures for influenza and monitoring any subsequent changes in hospitalization rates.

Oncogenic Ras and ΔNp63α cooperate to recruit immunosuppressive polymorphonuclear myeloid-derived suppressor cells in a mouse model of squamous cancer pathogenesis.

Introduction: Amplification of human chromosome 3q26-29, which encodes oncoprotein ΔNp63 among other isoforms of the p63 family, is a feature common to squamous cell carcinomas (SCCs) of multiple tissue origins. Along with overexpression of ΔNp63, activation of the protooncogene, RAS, whether by overexpression or oncogenic mutation, is frequently observed in many cancers. In this study, analysis of transcriptome data from The Cancer Genome Atlas (TCGA) demonstrated that expression of TP63 mRNA, particularly ΔNp63 isoforms, and HRAS are significantly elevated in advanced squamous cell carcinomas of the head and neck (HNSCCs), suggesting pathological significance. However, how co-overexpressed ΔNp63 and HRAS affect the immunosuppressive tumor microenvironment (TME) is incompletely understood. Methods: Here, we established and characterized an immune competent mouse model using primary keratinocytes with retroviral-mediated overexpression of ΔNp63α and constitutively activated HRAS (v-rasHa G12R) to evaluate the role of these oncogenes in the immune TME. Results: In this model, orthotopic grafting of wildtype syngeneic keratinocytes expressing both v-rasHa and elevated levels of ΔNp63α consistently yield carcinomas in syngeneic hosts, while cells expressing v-rasHa alone yield predominantly papillomas. We found that polymorphonuclear (PMN) myeloid cells, experimentally validated to be immunosuppressive and thus representing myeloid-derived suppressor cells (PMN-MDSCs), were significantly recruited into the TME of carcinomas arising early following orthotopic grafting of ΔNp63α/v-rasHa-expressing keratinocytes. ΔNp63α/v-rasHa-driven carcinomas expressed higher levels of chemokines implicated in recruitment of MDSCs compared to v-rasHa-initiated tumors, providing a heretofore undescribed link between ΔNp63α/HRAS-driven carcinomas and the development of an immunosuppressive TME. Conclusion: These results support the utilization of a genetic carcinogenesis model harboring specific genomic drivers of malignancy to study mechanisms underlying the development of local immunosuppression.

Codetections of Other Respiratory Viruses Among Children Hospitalized With COVID-19.

OBJECTIVES: To assess the clinical impact of respiratory virus codetections among children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: During March 2020 to February 2022, the US coronavirus disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET) identified 4372 children hospitalized with SARS-CoV-2 infection admitted primarily for fever, respiratory illness, or presumed COVID-19. We compared demographics, clinical features, and outcomes between those with and without codetections who had any non-SARS-CoV-2 virus testing. Among a subgroup of 1670 children with complete additional viral testing, we described the association between presence of codetections and severe respiratory illness using age-stratified multivariable logistic regression models. RESULTS: Among 4372 children hospitalized, 62% had non-SARS-CoV-2 respiratory virus testing, of which 21% had a codetection. Children with codetections were more likely to be <5 years old (yo), receive increased oxygen support, or be admitted to the ICU (P < .001). Among children <5 yo, having any viral codetection (<2 yo: adjusted odds ratio [aOR] 2.1 [95% confidence interval [CI] 1.5-3.0]; 2-4 yo: aOR 1.9 [95% CI 1.2-3.1]) or rhinovirus/enterovirus codetection (<2 yo: aOR 2.4 [95% CI 1.6-3.7]; 2-4: aOR 2.4 [95% CI 1.2-4.6]) was significantly associated with severe illness. Among children <2 yo, respiratory syncytial virus (RSV) codetections were also significantly associated with severe illness (aOR 1.9 [95% CI 1.3-2.9]). No significant associations were seen among children ≥5 yo. CONCLUSIONS: Respiratory virus codetections, including RSV and rhinovirus/enterovirus, may increase illness severity among children <5 yo hospitalized with SARS-CoV-2 infection.