Exposure to the persistent organic pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) disrupts development of the zebrafish inner ear.

Dioxins are a class of highly toxic and persistent environmental pollutants that have been shown through epidemiological and laboratory-based studies to act as developmental teratogens. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent dioxin congener, has a high affinity for the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. TCDD-induced AHR activation during development impairs nervous system, cardiac, and craniofacial development. Despite the robust phenotypes previously reported, the characterization of developmental malformations and our understanding of the molecular targets mediating TCDD-induced developmental toxicity remains limited. In zebrafish, TCDD-induced craniofacial malformations are produced, in part, by the downregulation of SRY-box transcription factor 9b (sox9b), a member of the SoxE gene family. sox9b, along with fellow SoxE gene family members sox9a and sox10, have important functions in the development of the otic placode, the otic vesicle, and, ultimately, the inner ear. Given that sox9b is a known target of TCDD and that transcriptional interactions exist among SoxE genes, we asked whether TCDD exposure impaired the development of the zebrafish auditory system, specifically the otic vesicle, which gives rise to the sensory components of the inner ear. Using immunohistochemistry, in vivo confocal imaging, and time-lapse microscopy, we assessed the impact of TCDD exposure on zebrafish otic vesicle development. We found exposure resulted in structural deficits, including incomplete pillar fusion and altered pillar topography, leading to defective semicircular canal development. The observed structural deficits were accompanied by reduced collagen type II expression in the ear. Together, our findings reveal the otic vesicle as a novel target of TCDD-induced toxicity, suggest that the function of multiple SoxE genes may be affected by TCDD exposure, and provide insight into how environmental contaminants contribute to congenital malformations.

Exposure to the persistent organic pollutant 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) disrupts development of the zebrafish inner ear.

Dioxins are a class of highly toxic and persistent environmental pollutants that have been shown through epidemiological and laboratory-based studies to act as developmental teratogens. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent dioxin congener, has a high affinity for the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. TCDD-induced AHR activation during development impairs nervous system, cardiac, and craniofacial development. Despite the robust phenotypes previously reported, the characterization of developmental malformations and our understanding of the molecular targets mediating TCDD-induced developmental toxicity remains limited. In zebrafish, TCDD-induced craniofacial malformations are produced, in part, by the downregulation of SRY-box transcription factor 9b ( sox9b ), a member of the SoxE gene family. sox9b , along with fellow SoxE gene family members sox9a and sox10 , have important functions in the development of the otic placode, the otic vesicle, and, ultimately, the inner ear. Given that sox9b in a known target of TCDD and that transcriptional interactions exist among SoxE genes, we asked whether TCDD exposure impaired the development of the zebrafish auditory system, specifically the otic vesicle, which gives rise to the sensory components of the inner ear. Using immunohistochemistry, in vivo confocal imaging, and time-lapse microscopy, we assessed the impact of TCDD exposure on zebrafish otic vesicle development. We found exposure resulted in structural deficits, including incomplete pillar fusion and altered pillar topography, leading to defective semicircular canal development. The observed structural deficits were accompanied by reduced collagen type II expression in the ear. Together, our findings reveal the otic vesicle as a novel target of TCDD-induced toxicity, suggest that the function of multiple SoxE genes may be affected by TCDD exposure, and provide insight into how environmental contaminants contribute to congenital malformations. Highlights: The zebrafish ear is necessary to detect changes in motion, sound, and gravity.Embryos exposed to TCDD lack structural components of the developing ear.TCDD exposure impairs formation of the fusion plate and alters pillar topography.The semicircular canals of the ear are required to detect changes in movement.Following TCDD exposure embryos fail to establish semicircular canals.

Emergency Absentee Voting for Hospitalized Patients and Voting During COVID-19: A 50-State Study.

INTRODUCTION: Voters facing illness or disability are disproportionately under-represented in terms of voter turnout. Earlier research has indicated that enfranchisement of these populations may reinforce the implementation of policies improving health outcomes and equity. Due to the confluence of the coronavirus 2019 (COVID-19) pandemic and the 2020 election, we aimed to assess emergency absentee voting processes, which allow voters hospitalized after regular absentee deadlines to still obtain an absentee ballot, and election changes due to COVID-19 in all 50 states. METHODS: We performed a cross-sectional study collecting 34 variables pertaining to emergency voting processes and COVID-19-related election changes, including deadlines, methods of submission for applications and ballots, and specialized services for patients. Data were obtained from, in order of priority, state boards of elections websites, poll worker manuals, application forms, and state legislation. We verified all data through direct correspondence with state boards of elections. RESULTS: Emergency absentee voting processes are in place in 39 states, with the remaining states having universal vote-by-mail (n = 5) or extended regular absentee voting deadlines (n = 6). The emergency absentee period most commonly began within 24 hours following the normal absentee application deadline, which was often seven days before an election (n = 11). Unique aspects of emergency voting processes included patients designating an "authorized agent" to deliver their applications and ballots (n = 38), electronic ballot delivery (n = 5), and in-person teams that deliver ballots directly to patients (n = 18). Documented barriers in these processes nationwide include unavailable online information (n = 11), restrictions mandating agents to be family members (n = 7), physician affidavits or signatures (n = 9), and notary or witness signature requirements (n = 15). For the November 2020 presidential election, 12 states expanded absentee eligibility to allow COVID-19 as a reason to request an absentee ballot, and 18 states mailed absentee ballot applications or absentee ballots to all registered voters. CONCLUSION: While 39 states operate emergency absentee voting processes for hospitalized voters, there are considerable areas for improvement and heterogeneity in guidelines for these protocols. For future election cycles, information on emergency voting and broader election reforms due to COVID-19 may be useful for emergency providers and patients alike to improve the democratic participation of voters experiencing illness.

Emergency Mail-in Voting in Rhode Island: Protecting Civic Participation During COVID-19 and Beyond.

The COVID-19 pandemic challenges safe and equitable voting in the United States' 2020 elections, and in response, several states including Rhode Island (RI) have made significant changes to election policy. In addition to increasing accessibility of mail-in voting by mailing applications to all registered voters, RI has suspended their notary/witness requirement for both the primary and general election. However, RI's "emergency" voting process still plays a crucial role in allowing voters who missed the mail-in ballot application deadline, such as those unexpectedly hospitalized in the days leading up to the election, to still cast their ballot. COVID-19 has also forced RI to modify its emergency voting procedures, most notably allowing healthcare workers to serve on bipartisan ballot delivery teams. This commentary highlights these salient updates to voting procedures and serves as a primer as to how interested health care workers may navigate this process alongside patients and lead in the arena of patient voting rights.

CCL21 is an effective surgical neoadjuvant for treatment of mammary tumors.

In previous studies, the chemokine CCL21 has shown biological activities that include T cell, natural killer (NK) cell, and dendritic cell (DC) chemoattraction. The goal of this study was to determine the effects of administering CCL21 to orthotopic mammary tumors in terms of impact on tumor growth rate, immune cell infiltration of the primary tumor and survival. We found that a single intratumoral administration of CCL21 slowed the growth of orthotopic mammary tumors and increased intratumoral infiltration by T cells, NK cells and DCs. CCL21 intratumoral administration also prolonged the survival of tumor-earing mice. Furthermore, mice that received intratumoral neoadjuvant CCL21 ior to surgical resection of tumors survived significantly longer than control mice. The urviving neoadjuvant CCL21-reated mice, when challenged again with cl-6, had significantly slower rate of tumor growth than challenged control mice. Thus, our ata indicate that CCL21 treatment prior to mammary tumor resection can significantly rolong survival and increase resistance to subsequent tumor challenge. Overall, our indings suggest that intratumoral administration of CCL21 has potential as a neoadjuvant mmunotherapy for breast cancer.

Synthesis of a new fluorescent probe specific for catechols.

[reaction: see text] The synthesis of a new fluorescent probe, specific for the catechol moiety, has been conducted by preparation of alpha,alpha-dibromomalonamides containing an appropriate fluorophore. N,N'-Bis-anthracen-9-ylmethyl-2,2-dibromomalonamide reacted with various catechols in the presence of cesium carbonate to generate highly fluorescent derivatives.