The shifting impact and response to COVID-19 in Florida.

The first cases of COVID-19 in Florida were diagnosed on March 1, 2020. Three years later, more than 7.3 million people have had COVID-19 in Florida, and more than 93,000 individuals have died from this illness. When considering the impact of COVID-19 on Florida, several key factors need to be considered, including that Florida was one of the most medically vulnerable states due to a substantial proportion of older individuals and those with underlying medical conditions. Florida also has a centralized Department of Health and Division of Emergency Management structure that facilitated response activities. Looking at the impact of COVID-19 on Florida, two distinct phases need to be considered: the pre-Delta variant phase from March 2020 to July 2021 and the Delta variant and beyond phase that began July 2021 and still continues. During the 16-month first phase, about 38,000 people died. Yet, 24,000 people died during the 5-months of the Delta variant wave from July to November 2021. During the Omicron waves that followed Delta, an additional 31,000 people died. Florida thus went from ranking 26th in death per capita in the United States at the end of the first phase to 10th a few months into the Delta wave and now ranks 8th. Why did these phases differ so dramatically in terms of mortality? During the first phase of the pandemic, adherence to established nonpharmacological and older adult protection measures was recommended. When COVID-19 vaccines became available in December 2020, there was an aggressive campaign to promote COVID-19 vaccination, and public acceptance was high. The second phase followed political opposition to CDC and public health expert guidelines, the rise of anti-vaccine sentiment and misinformation, and falling vaccination rates. These factors contributed to considerable population vulnerability to severe disease when the Delta variant hit. As the former State Surgeon General and Secretary of Health of Florida from June 2019 to September 2021, this report provides perspective on the shifting impact and response to COVID-19 in Florida, which is the third most populous state in the United States. This perspective shows the clear consequences of shifting from standard public health practices and vaccine promotion to attacks on public health and vaccines.

Approach to the Patient: Management and the Long-term Consequences of Graves' Disease in Children.

In children, Graves' disease (GD) is the most common cause of hyperthyroidism. Most pediatric patients with GD will not go into lasting remission, even following many years of antidrug therapy. Thus, most pediatric patients will require radioactive iodine (RAI) or surgery. When antithyroid drugs are used, methimazole is the drug of choice. When methimazole is used in children, up to 20% will have minor adverse reactions and serious adverse events occur in up to 1%. RAI is an effective form of therapy when the thyroid size is less than 80 g. Because of concerns of whole-body radiation exposure, it is recommended that RAI be avoided in children under 5 years of age, and dosages less than 10 mCi be used between 5 and 10 years of age. Surgery is an effective treatment in children if performed by a high-volume thyroid surgeon. Because of the scarcity of high-volume pediatric thyroid surgeons, a multidisciplinary approach using pediatric surgeons and endocrine surgeons can be considered. Whereas there is a trend toward long-term antithyroid drug therapy in adults, for several reasons, this approach may not be practical for children. Determining the optimal treatment for the pediatric patient with GD, requires consideration of the risks and benefits relating to age and likelihood of remission.

Knockdown of DNA methyltransferase 1 reduces DNA methylation and alters expression patterns of cardiac genes in embryonic cardiomyocytes.

We previously found that DNA methyltransferase 3a (DNMT3a) plays an important role in regulating embryonic cardiomyocyte gene expression, morphology, and function. In this study, we investigated the role of the most abundant DNMT in mammalian cells, DNMT1, in these processes. It is known that DNMT1 is essential for embryonic development, during which it is involved in regulating cardiomyocyte DNA methylation and gene expression. We used siRNA to knock down DNMT1 expression in primary cultures of mouse embryonic cardiomyocytes. Immunofluorescence staining and multielectrode array were, respectively, utilized to evaluate cardiomyocyte growth and electrophysiology. RNA sequencing (RNA-Seq) and multiplex bisulfite sequencing were, respectively, performed to examine gene expression and promoter methylation. At 72 h post-transfection, reduction of DNMT1 expression decreased the number and increased the size of embryonic cardiomyocytes. Beat frequency and the amplitude of field action potentials were decreased by DNMT1 siRNA. RNA-Seq analysis identified 801 up-regulated genes and 494 down-regulated genes in the DNMT1 knockdown cells when compared to controls. Pathway analysis of the differentially expressed genes revealed pathways that were associated with cell death and survival, cell morphology, cardiac function, and cardiac disease. Alternative splicing analysis identified 929 differentially expressed exons, including 583 up-regulated exons and 308 down-regulated exons. Moreover, decreased methylation levels were found in the promoters of cardiac genes Myh6, Myh7, Myh7b, Tnnc1, Tnni3, Tnnt2, Nppa, Nppb, mef2c, mef2d, Camta2, Cdkn1A, and Cdkn1C. Of these 13 genes, 6 (Myh6, Tnnc1, Tnni3, Tnnt2, Nppa, Nppb) and 1 (Cdkn1C) had increased or decreased gene expression, respectively. Altogether, these data show that DNMT1 is important in embryonic cardiomyocytes by regulating DNA methylation, gene expression, gene splicing, and cell function.

SARS-COV-2 ANTIBODY PREVALENCE AMONG HEALTHCARE WORKERS AND FIRST RESPONDERS, FLORIDA, MAY-JUNE 2020.

BACKGROUND: The SARS-CoV-2 virus responsible for severe respiratory infection associated with coronavirus disease 2019 (COVID-19) was first confirmed in Florida on March 1, 2020. Responding to the pandemic, multi-agency collaborative partnerships put in place actions integrating point-of-care antibody testing at established large-scale COVID-19 testing sites where the baseline seropositivity of COVID-19 in health care workers and first responders in Florida at the start of the pandemic was established. PURPOSE: Determine the seropositivity of healthcare workers and first responders at five drive thru testing sites using a rapid SARS-CoV-2 antibody test in Florida from May 6 through June 3, 2020. METHODS: The first drive-thru SARS-CoV-2 antibody test site was opened at Miami Hard Rock Stadium, May 6, 2020. Testing expanded to three additional sites on May 9, 2020: Jacksonville, Orlando, and Palm Beach. The fifth and final site, Miami Beach, began testing on May 21, 2020. Healthcare workers and first responder's self-seeking SARS-CoV-2 testing were designated for antibody testing and completed a laboratory collection form onsite for the point-of-care test. All testing was performed on whole blood specimens (obtained by venipuncture) using the Cellex Inc. qSARS-CoV-2 IgG/IgM Rapid Test. Seropositivity was assessed by univariate analysis and by logistic regression including the covariates age, sex, race/ethnicity, and testing location. RESULTS AND DISCUSSION: As of June 3, 2020, of 5,779 healthcare workers and first responders tested, 4.1% were seropositive (range 2.6-8.2%). SARS-COV-2 antibody tests had higher odds of being positive for persons testing at the Miami Hard Rock Stadium (aOR 2.24 [95% C.I. 1.48-3.39]), persons of Haitian/Creole ethnicity (aOR 3.28 [95% C.I. 1.23-8.72]), Hispanic/Latino(a) ethnicity (aOR 2.17 [95% C.I. 1.50-3.13], and Black non-Hispanic persons (aOR 1.63 [95% C.I. 1.08-2.46]). SARS-COV-2 antibody prevalence among first responders and healthcare workers in five sites in Florida varied by race and ethnicity and by testing location.

COVID-19 in Primary and Secondary School Settings During the First Semester of School Reopening - Florida, August-December 2020.

After detection of cases of COVID-19 in Florida in March 2020, the governor declared a state of emergency on March 9,* and all school districts in the state suspended in-person instruction by March 20. Most kindergarten through grade 12 (K-12) public and private schools in Florida reopened for in-person learning during August 2020, with varying options for remote learning offered by school districts. During August 10-December 21, 2020, a total of 63,654 COVID-19 cases were reported in school-aged children; an estimated 60% of these cases were not school-related. Fewer than 1% of registered students were identified as having school-related COVID-19 and <11% of K-12 schools reported outbreaks. District incidences among students correlated with the background disease incidence in the county; resumption of in-person education was not associated with a proportionate increase in COVID-19 among school-aged children. Higher rates among students were observed in smaller districts, districts without mandatory mask-use policies, and districts with a lower proportion of students participating in remote learning. These findings highlight the importance of implementing both community-level and school-based strategies to reduce the spread of COVID-19 and suggest that school reopening can be achieved without resulting in widespread illness among students in K-12 school settings.

The Florida Department of Health STEPS Public Health Approach: The COVID-19 Response Plan and Outcomes Through May 31, 2020.

In January 2020, the Florida Department of Health began planning for a potential coronavirus disease 2019 (COVID-19) outbreak. The first 2 cases of COVID-19 in Florida were confirmed on March 1, 2020. The state's multiagency response to the COVID-19 pandemic was based on the Florida STEPS plan: (1) social distancing, (2) testing and contact tracing, (3) elderly and medically vulnerable population protection, (4) preparing hospitals for a patient surge and health care worker protection, and (5) stopping the introduction of COVID-19 into the state. This brief report describes COVID-19 response strategies and outcomes in Florida through May 31, 2020.

Clinical considerations for the treatment of secondary differentiated thyroid carcinoma in childhood cancer survivors.

The incidence of differentiated thyroid carcinoma (DTC) has increased rapidly over the past several years. Thus far, the only conclusively established risk factor for developing DTC is exposure to ionizing radiation, especially when the exposure occurs in childhood. Since the number of childhood cancer survivors (CCS) is increasing due to improvements in treatment and supportive care, the number of patients who will develop DTC after surviving childhood cancer (secondary thyroid cancer) is also expected to rise. Currently, there are no recommendations for management of thyroid cancer specifically for patients who develop DTC as a consequence of cancer therapy during childhood. Since complications or late effects from prior cancer treatment may elevate the risk of toxicity from DTC therapy, the medical history of CCS should be considered carefully in choosing DTC treatment. In this paper, we emphasize how the occurrence and treatment of the initial childhood malignancy affects the medical and psychosocial factors that will play a role in the diagnosis and treatment of a secondary DTC. We present considerations for clinicians to use in the management of patients with secondary DTC, based on the available evidence combined with experience-based opinions of the authors.

Bumetanide increases Cl--dependent short-circuit current in late distal colon: Evidence for the presence of active electrogenic Cl- absorption.

Mammalian colonic epithelia consist of cells that are capable of both absorbing and secreting Cl-. The present studies employing Ussing chamber technique identified two opposing short-circuit current (Isc) responses to basolateral bumetanide in rat distal colon. Apart from the transepithelial Cl--secretory Isc in early distal colon that was inhibited by bumetanide, bumetanide also stimulated Isc in late distal colon that had not previously been identified. Since bumetanide inhibits basolateral Na+-K+-2Cl- cotransporter (NKCC) in crypt cells and basolateral K+-Cl- cotransporter (KCC) in surface epithelium, we proposed this stimulatory Isc could represent a KCC-mediated Cl- absorptive current. In support of this hypothesis, ion substitution experiments established Cl- dependency of this absorptive Isc and transport inhibitor studies demonstrated the involvement of an apical Cl- conductance. Current distribution and RNA sequencing analyses revealed that this Cl- absorptive Isc is closely associated with epithelial Na+ channel (ENaC) but is not dependent on ENaC activity. Thus, inhibition of ENaC by 10 µM amiloride or benzamil neither altered the direction nor its activity. Physiological studies suggested that this Cl- absorptive Isc senses dietary Cl- content; thus when dietary Cl- was low, Cl- absorptive Isc was up-regulated. In contrast, when dietary Cl- was increased, Cl- absorptive Isc was down-regulated. We conclude that an active Cl- extrusion mechanism exists in ENaC-expressing late distal colon and likely operates in parallel with ENaC to facilitate NaCl absorption.

Long-term consequences of disrupting adenosine signaling during embryonic development.

There is growing evidence that disruption in the prenatal environment can have long-lasting effects on an individual's health in adulthood. Research on the fetal programming of adult diseases, including cardiovascular disease, focuses on epi-mutations, which alter the normal pattern of epigenetic factors such as DNA methylation, miRNA expression, or chromatin modification, rather than traditional genetic alteration. Thus, understanding how in utero chemical exposures alter epigenetics and lead to adult disease is of considerable public health concern. Few signaling molecules have the potential to influence the developing mammal as the nucleoside adenosine. Adenosine levels increase rapidly with tissue hypoxia and inflammation. Adenosine antagonists including the methlyxanthines caffeine and theophylline are widely consumed during pregnancy. The receptors that transduce adenosine action are the A1, A2a, A2b, and A3 adenosine receptors (ARs). We examined the long-term effects of in utero disruption of adenosine signaling on cardiac gene expression, morphology, and function in adult offspring. One substance that fetuses are frequently exposed to is caffeine, which is a non-selective adenosine receptor antagonist. Over the past several years, we examined the role of adenosine signaling during embryogenesis and cardiac development. We discovered that in utero alteration in adenosine action leads to adverse effects on embryonic and adult murine hearts. We find that cardiac A1ARs protect the embryo from in utero hypoxic stress, a condition that causes an increase in adenosine levels. After birth in mice, we observed that in utero caffeine exposure leads to abnormal cardiac function and morphology in adults, including an impaired response to ß-adrenergic stimulation. Recently, we observed that in utero caffeine exposure induces transgenerational effects on cardiac morphology, function, and gene expression. Our findings indicate that the effects of altered adenosine signaling are dependent on signaling through the A1ARs and timing of disruption. In addition, the long-term effects of altered adenosine signaling appear to be mediated by alterations in DNA methylation, an epigenetic process critical for normal development.