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1.
MMWR Morb Mortal Wkly Rep ; 72(40): 1089-1094, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37796744

ABSTRACT

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.


Subject(s)
COVID-19 , Humans , Adult , United States/epidemiology , COVID-19/epidemiology , COVID-19/therapy , SARS-CoV-2 , Hospitalization , Intensive Care Units , Vaccination
2.
Dev Psychobiol ; 65(5): e22394, 2023 07.
Article in English | MEDLINE | ID: mdl-37338257

ABSTRACT

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.


Subject(s)
Affect , Mother-Child Relations , Respiratory Sinus Arrhythmia , Adult , Child , Female , Humans , Mothers , Respiratory Sinus Arrhythmia/physiology , Hispanic or Latino , Black or African American , Child, Preschool
3.
Heart Fail Rev ; 27(3): 903-913, 2022 05.
Article in English | MEDLINE | ID: mdl-33661404

ABSTRACT

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.


Subject(s)
Cardiomyopathies , Heart Failure , Heart Transplantation , Heart-Assist Devices , Thrombosis , Cardiomyopathies/complications , Child , Heart Failure/epidemiology , Heart Failure/etiology , Heart Failure/therapy , Heart Transplantation/adverse effects , Heart-Assist Devices/adverse effects , Humans , Retrospective Studies , Thrombosis/epidemiology , Thrombosis/etiology , Treatment Outcome
4.
MMWR Morb Mortal Wkly Rep ; 71(34): 1085-1091, 2022 08 26.
Article in English | MEDLINE | ID: mdl-36006841

ABSTRACT

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).


Subject(s)
COVID-19 , SARS-CoV-2 , Adolescent , Adult , COVID-19/epidemiology , COVID-19/therapy , COVID-19 Vaccines , Hospitalization , Humans , United States/epidemiology , Vaccination
5.
MMWR Morb Mortal Wkly Rep ; 71(7): 271-278, 2022 Feb 18.
Article in English | MEDLINE | ID: mdl-35176003

ABSTRACT

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.*.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Hospitalization/trends , SARS-CoV-2 , Vaccination/statistics & numerical data , Adolescent , Child , Child, Preschool , Humans , Incidence , Infant , Population Surveillance , United States/epidemiology
6.
MMWR Morb Mortal Wkly Rep ; 70(23): 851-857, 2021 Jun 11.
Article in English | MEDLINE | ID: mdl-34111061

ABSTRACT

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.†.


Subject(s)
COVID-19/diagnosis , COVID-19/therapy , Hospitalization/statistics & numerical data , Laboratories , SARS-CoV-2/isolation & purification , Adolescent , COVID-19/epidemiology , Child , Female , Humans , Male , United States/epidemiology
7.
Nurs Adm Q ; 45(4): 346-352, 2021.
Article in English | MEDLINE | ID: mdl-34320532

ABSTRACT

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.


Subject(s)
Contact Tracing/methods , Faculty, Nursing/organization & administration , Leadership , Universities/organization & administration , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Testing/methods , Cooperative Behavior , Humans , Pandemics , SARS-CoV-2 , Student Health Services/organization & administration , Students
8.
MMWR Morb Mortal Wkly Rep ; 69(38): 1369-1373, 2020 Sep 25.
Article in English | MEDLINE | ID: mdl-32970656

ABSTRACT

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.


Subject(s)
Clinical Laboratory Techniques/statistics & numerical data , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Health Status Disparities , Healthcare Disparities/statistics & numerical data , Hospitalization/statistics & numerical data , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Poverty Areas , Adult , Aged , COVID-19 , COVID-19 Testing , Coronavirus Infections/diagnosis , Humans , Incidence , Middle Aged , Risk Factors , Utah/epidemiology , Young Adult
9.
MMWR Morb Mortal Wkly Rep ; 69(15): 458-464, 2020 04 17.
Article in English | MEDLINE | ID: mdl-32298251

ABSTRACT

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.


Subject(s)
COVID-19 , Diabetes Mellitus , Humans , Male , United States/epidemiology , Aged , Female , COVID-19/epidemiology , COVID-19/therapy , SARS-CoV-2 , Population Surveillance , Hospitalization
10.
MMWR Morb Mortal Wkly Rep ; 69(38): 1347-1354, 2020 Sep 25.
Article in English | MEDLINE | ID: mdl-32970655

ABSTRACT

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.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Pregnancy Complications, Infectious/therapy , Pregnancy Complications, Infectious/virology , Pregnancy Outcome/epidemiology , Adolescent , Adult , Asymptomatic Diseases/epidemiology , COVID-19 , Coronavirus Infections/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Laboratories, Hospital , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2 , United States/epidemiology , Young Adult
11.
J Cell Sci ; 130(12): 2018-2025, 2017 Jun 15.
Article in English | MEDLINE | ID: mdl-28455412

ABSTRACT

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.


Subject(s)
Amphiregulin/genetics , Cell Lineage , Cellular Reprogramming , Epithelial Cells/cytology , Signal Transduction , Animals , Cell Differentiation , Cell Proliferation , Cell Transplantation , Cerebral Cortex/embryology , Embryonic Stem Cells/cytology , Estrogen Receptor alpha/genetics , Estrogens/metabolism , Female , Green Fluorescent Proteins/metabolism , Male , Mammary Glands, Animal/cytology , Mice , Mice, Nude , Mice, Transgenic , Neural Stem Cells/cytology , Pregnancy , Spermatozoa/metabolism , Testis/metabolism
12.
Mol Carcinog ; 58(9): 1571-1580, 2019 09.
Article in English | MEDLINE | ID: mdl-31286584

ABSTRACT

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.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Epithelial Cells/metabolism , Homeostasis/physiology , NF-kappa B/metabolism , Signal Transduction/physiology , Tumor Suppressor Proteins/metabolism , Animals , Carcinoma, Squamous Cell/pathology , Epithelial Cells/pathology , Humans , Tumor Microenvironment/physiology
13.
Int J Mol Sci ; 20(14)2019 Jul 23.
Article in English | MEDLINE | ID: mdl-31340447

ABSTRACT

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.


Subject(s)
Carcinoma, Squamous Cell/genetics , Epithelial Cells/metabolism , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , Lung Neoplasms/genetics , Skin Neoplasms/genetics , Transcription Factors/genetics , Tumor Suppressor Proteins/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Adhesion , Cell Lineage/genetics , Cell Movement , Cell Proliferation , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Epidermis/metabolism , Epidermis/pathology , Epithelial Cells/pathology , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Signal Transduction , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , Transcription Factors/metabolism , Tumor Suppressor Proteins/metabolism
14.
Clin Infect Dis ; 65(8): 1289-1297, 2017 10 15.
Article in English | MEDLINE | ID: mdl-28525597

ABSTRACT

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.


Subject(s)
Influenza Vaccines/immunology , Influenza, Human/epidemiology , Influenza, Human/physiopathology , Vaccination/statistics & numerical data , Adolescent , Adult , Aged , Female , Humans , Influenza, Human/prevention & control , Male , Middle Aged , Propensity Score , Retrospective Studies , Severity of Illness Index , United States/epidemiology , Young Adult
15.
J Mammary Gland Biol Neoplasia ; 20(1-2): 93-101, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26362796

ABSTRACT

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.


Subject(s)
Cell Differentiation , Epithelial Cells/metabolism , Mammary Glands, Animal/growth & development , Mammary Glands, Animal/metabolism , Signal Transduction , Stem Cells/metabolism , Amphiregulin/metabolism , Animals , Cell Proliferation , Estrogens/metabolism , Mice , Progesterone/metabolism , Prolactin/metabolism , Receptors, Progesterone/metabolism , Stem Cells/physiology
16.
Anxiety Stress Coping ; 37(1): 100-113, 2024 01.
Article in English | MEDLINE | ID: mdl-37075162

ABSTRACT

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.


Subject(s)
Anxiety , Arrhythmias, Cardiac , Cognition , Mothers , Politics , Stress, Psychological , Female , Humans , Anxiety/psychology , Arrhythmias, Cardiac/epidemiology , Hispanic or Latino , Black or African American , Southeastern United States , Stress, Psychological/epidemiology
17.
Front Immunol ; 14: 1200970, 2023.
Article in English | MEDLINE | ID: mdl-37638000

ABSTRACT

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.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Myeloid-Derived Suppressor Cells , Humans , Animals , Mice , Carcinoma, Squamous Cell/genetics , Immunosuppressive Agents , Squamous Cell Carcinoma of Head and Neck , Disease Models, Animal , Tumor Microenvironment/genetics
18.
Pediatrics ; 151(2)2023 02 01.
Article in English | MEDLINE | ID: mdl-36995184

ABSTRACT

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.


Subject(s)
COVID-19 , Respiratory Tract Infections , SARS-CoV-2 , Humans , Male , Female , Child, Preschool , Child , COVID-19/diagnosis , COVID-19/epidemiology , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Hospitalization , Coinfection , SARS-CoV-2/isolation & purification , Viruses , Infant , Adolescent , Cross-Sectional Studies
19.
Lancet Microbe ; 4(11): e903-e912, 2023 11.
Article in English | MEDLINE | ID: mdl-37769676

ABSTRACT

BACKGROUND: Influenza burden varies across seasons, partly due to differences in circulating influenza virus types or subtypes. Using data from the US population-based surveillance system, Influenza Hospitalization Surveillance Network (FluSurv-NET), we aimed to assess the severity of influenza-associated outcomes in individuals hospitalised with laboratory-confirmed influenza virus infections during the 2010-11 to 2018-19 influenza seasons. METHODS: To evaluate the association between influenza virus type or subtype causing the infection (influenza A H3N2, A H1N1pdm09, and B viruses) and in-hospital severity outcomes (intensive care unit [ICU] admission, use of mechanical ventilation or extracorporeal membrane oxygenation [ECMO], and death), we used FluSurv-NET to capture data for laboratory-confirmed influenza-associated hospitalisations from the 2010-11 to 2018-19 influenza seasons for individuals of all ages living in select counties in 13 US states. All individuals had to have an influenza virus test within 14 days before or during their hospital stay and an admission date between Oct 1 and April 30 of an influenza season. Exclusion criteria were individuals who did not have a complete chart review; cases from sites that contributed data for three or fewer seasons; hospital-onset cases; cases with unidentified influenza type; cases of multiple influenza virus type or subtype co-infection; or individuals younger than 6 months and ineligible for the influenza vaccine. Logistic regression models adjusted for influenza season, influenza vaccination status, age, and FluSurv-NET site compared odds of in-hospital severity by virus type or subtype. When missing, influenza A subtypes were imputed using chained equations of known subtypes by season. FINDINGS: Data for 122 941 individuals hospitalised with influenza were captured in FluSurv-NET from the 2010-11 to 2018-19 seasons; after exclusions were applied, 107 941 individuals remained and underwent influenza A virus imputation when missing A subtype (43·4%). After imputation, data for 104 969 remained and were included in the final analytic sample. Averaging across imputed datasets, 57·7% (weighted percentage) had influenza A H3N2, 24·6% had influenza A H1N1pdm09, and 17·7% had influenza B virus infections; 16·7% required ICU admission, 6·5% received mechanical ventilation or ECMO, and 3·0% died (95% CIs had a range of less than 0·1% and are not displayed). Individuals with A H1N1pdm09 had higher odds of in-hospital severe outcomes than those with A H3N2: adjusted odds ratios (ORs) for A H1N1pdm09 versus A H3N2 were 1·42 (95% CI 1·32-1·52) for ICU admission; 1·79 (1·60-2·00) for mechanical ventilation or ECMO use; and 1·25 (1·07-1·46) for death. The adjusted ORs for individuals infected with influenza B versus influenza A H3N2 were 1·06 (95% CI 1·01-1·12) for ICU admission, 1·14 (1·05-1·24) for mechanical ventilation or ECMO use, and 1·18 (1·07-1·31) for death. INTERPRETATION: Despite a higher burden of hospitalisations with influenza A H3N2, we found an increased likelihood of in-hospital severe outcomes in individuals hospitalised with influenza A H1N1pdm09 or influenza B virus. Thus, it is important for individuals to receive an annual influenza vaccine and for health-care providers to provide early antiviral treatment for patients with suspected influenza who are at increased risk of severe outcomes, not only when there is high influenza A H3N2 virus circulation but also when influenza A H1N1pdm09 and influenza B viruses are circulating. FUNDING: The US Centers for Disease Control and Prevention.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza Vaccines , Influenza, Human , Humans , United States/epidemiology , Influenza, Human/therapy , Influenza, Human/prevention & control , Cross-Sectional Studies , Influenza A Virus, H3N2 Subtype , Influenza B virus , Hospitalization
20.
Open Forum Infect Dis ; 10(12): ofad599, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38130595

ABSTRACT

Background: Older age and chronic conditions are associated with severe influenza outcomes; however, data are only comprehensively available for adults ≥65 years old. Using data from the Influenza Hospitalization Surveillance Network (FluSurv-NET), we identified characteristics associated with severe outcomes in adults 18-49 years old hospitalized with influenza. Methods: We included FluSurv-NET data from nonpregnant adults 18-49 years old hospitalized with laboratory-confirmed influenza during the 2011-2012 through 2018-2019 seasons. We used bivariate and multivariable logistic regression to determine associations between select characteristics and severe outcomes including intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. Results: A total of 16 140 patients aged 18-49 years and hospitalized with influenza were included in the analysis; the median age was 39 years, and 26% received current-season influenza vaccine before hospitalization. Obesity, asthma, and diabetes mellitus were the most common chronic conditions. Conditions associated with a significantly increased risk of severe outcomes included age group 30-39 or 40-49 years (IMV, age group 30-39 years: adjusted odds ratio [aOR], 1.25; IMV, age group 40-49 years: aOR, 1.36; death, age group 30-39 years: aOR, 1.28; death, age group 40-49 years: aOR, 1.69), being unvaccinated (ICU: aOR, 1.18; IMV: aOR, 1.25; death: aOR, 1.48), and having chronic conditions including extreme obesity and chronic lung, cardiovascular, metabolic, neurologic, or liver diseases (ICU: range aOR, 1.22-1.56; IMV: range aOR, 1.17-1.54; death: range aOR, 1.43-2.36). Conclusions: To reduce the morbidity and mortality associated with influenza among adults aged 18-49 years, health care providers should strongly encourage receipt of annual influenza vaccine and lifestyle/behavioral modifications, particularly among those with chronic medical conditions.

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