Qualitative Analysis of a Roundtable Exercise "Reflecting on the COVID-19 Experience of Public Health Professionals".

CONTEXT: Public health professionals around the country faced significant challenges responding to the COVID-19 pandemic. Reflecting on their experience is an essential element in making sense of their experience and learning from it. OBJECTIVE: The objective of this qualitative study was to (1) describe the lived experiences of public health professionals working during the COVID-19 pandemic, (2) discuss the effectiveness of a guided reflection exercise to help public health professionals process these experiences, and (3) provide lessons learned and best practices to inform preparation for a future infectious disease pandemic. DESIGN: Qualitative focus group study design. SETTING: This activity was conducted at a Midwestern state public health professional meeting. PARTICIPANTS: Forty-eight public health professionals self-selected to participate in this study. RESULTS: Five themes were elicited in this analysis, including Communication, Leadership and Collaboration, Data Management, Community Relationships, and Resources and Planning. In addition, public health professionals reported numerous lessons learned, including the need for more leadership from the state government, the conflicted response of their communities, and the benefits of community solidarity where it was present. CONCLUSIONS: This article provides a detailed account of public health workers' experiences during the COVID-19 pandemic. It also provides lessons learned that will help public health workers lead more effectively in the future. Guided reflection on a traumatic professional experience can assist participating individuals in making sense of their experience and learning important lessons from it.

Managing the Risk of COVID-19 Using Model Based Predictors: The Case of North Dakota.

OBJECTIVE: North Dakota (ND) had the highest coronavirus disease 2019 (COVID-19) case and mortality rate in the United States for nearly 2 mo. This study aims to compare 3 metrics ND used to guide public health action across its 53 counties. METHODS: Daily COVID-19 case and death totals in North Dakota were evaluated using data from the COVID-tracker website provided by the North Department of Health (NDDoH). It was reported as: active cases per 10,000, tests administered per 10,000, and test positivity rate (the North Dakota health metric). The COVID-19 Response press conferences provided data for the Governor's metric. The Harvard model used daily new cases per 100,000. A chi-squared test was used to compare differences in these 3 metrics on July 1, August 26, September 23, and November 13, 2020. RESULTS: On July 1, no significant difference between the metrics was found. By September 23, Harvard's health metric indicated critical risk while ND's health metric was moderate risk, and the Governor's metric was still low risk. CONCLUSIONS: ND's and the Governor's metric underrepresented the risk of the COVID-19 outbreak in North Dakota. The Harvard metric reflected North Dakota's increasing risk; it should be considered as a national standard in future pandemics. PUBLIC HEALTH IMPLICATIONS: Model-based predictors could guide policy-makers to effectively control spread of infectious disease; proactive models could reduce risk of disease as it progresses in vulnerable communities.

Evaluating the Association of Face Covering Mandates on COVID-19 Severity by State.

OBJECTIVE: During the COVID-19 pandemic in the United States, mitigation measures were implemented on a state-by-state basis. Governors were responsible for establishing interventions appropriate for their states and the timing of implementation. This paper evaluated the association between the presence and timing of a mask mandate and the severity of the COVID-19 epidemic by state. METHODS: The states were divided into 3 categories based on when the governors of each state implemented a mask mandate: Early (mask mandate implemented between March 2020 and June 2020), Late (July 2020-December 2020), and Never (no mask mandate implemented). The rates of hospitalizations and mortality (per 100 000) were assessed at the different time points during the pandemic across these categories from March to December 2020. RESULTS: The mortality rates across all 3 groups were observed to be highest in the beginning and toward the end of the pandemic in 2020 with the peak observed in the Early group between April and May 2020. Also, the rates of hospitalization increased steadily across all groups. The Early mask group was comprised of 86.7% and 13.3% states with Democratic and Republican governors respectively, and no states in the Never category had Democratic governors. CONCLUSION: These results support the benefit of implementing a mask mandate to minimize the impact of the COVID-19 pandemic and the role of political affiliation of governors on that impact.

The transmembrane src substrate Trask is an epithelial protein that signals during anchorage deprivation.

The roles of epithelial cells encompass both cellular- and tissue-level functions that involve numerous cell-cell and cell-matrix interactions, which ultimately mediate the highly structured arrangement of cells on a basement membrane. Although maintaining this basic structure is critical for preserving tissue integrity, plasticity in epithelial cell behavior is also critical for processes such as cell migration during development or wound repair, mitotic cell detachment, and physiological shedding. The mechanisms that mediate epithelial cell plasticity are only beginning to be understood. We previously identified Trask, a transmembrane protein that is phosphorylated by src kinases during mitosis. In this study, we report that the phosphorylation of Trask is associated with anchorage loss in epithelial cells. Phosphorylation of Trask is seen during the cell-detachment phase of mitosis, in experimentally induced interphase detachment, and during cell migration in experimental epithelial models. An analysis of human tissues shows that Trask is widely expressed in many epithelial tissues but not in most tissues of mesenchymal origin, except for a subset of early hematopoietic cells. Trask is not phosphorylated in epithelial tissues in vivo; however, its phosphorylation is seen in epithelial cells undergoing mitosis or physiological shedding. Trask is a novel epithelial membrane protein that is phosphorylated by src kinases when epithelial cells disengage from their tissue framework, identifying an important new regulator of epithelial tissue dynamics.

Medical Foods for Inborn Errors of Metabolism: History, Current Status, and Critical Need.

Successful intervention for inborn errors of metabolism (IEMs) is a triumph of modern medicine. For many of these conditions, medical foods are the cornerstone of therapy and the only effective interventions preventing disability or death. Medical foods are designed for patients with limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foods or nutrients, whereby dietary management cannot be achieved by modification of the normal diet alone. In the United States today, access to medical foods is not ensured for many individuals who are affected despite their proven efficacy in the treatment of IEMs, their universal use as the mainstay of IEM management, the endorsement of their use by professional medical organizations, and the obvious desire of families for effective care. Medical foods are not sufficiently covered by many health insurance plans in the United States and, without insurance coverage, many families cannot afford their high cost. In this review, we outline the history of medical foods, define their medical necessity, discuss the barriers to access and reimbursement resulting from the regulatory status of medical foods, and summarize previous efforts to improve access. The Advisory Committee on Heritable Disorders in Newborns and Children asserts that it is time to provide stable and affordable access to the effective management required for optimal outcomes through the life span of patients affected with IEMs. Medical foods as defined by the US Food and Drug Administration should be covered as required medical benefits for persons of all ages diagnosed with an IEM.

A genetic screen for Saccharomyces cerevisiae mutants affecting proteasome function, using a ubiquitin-independent substrate.

The great majority of proteasome substrates are marked for degradation by the attachment of polyubiquitin chains. Ornithine decarboxylase is degraded by the proteasome in the absence of this modification. We previously showed that this mechanism of degradation was conserved in eukaryotic cells. Here we use a reporter destabilized by mouse ornithine decarboxylase to screen non-essential Saccharomyces cerevisiae deletion mutants. We identified novel mutants that affect both ubiquitin-dependent and -independent proteasome degradation pathways. YLR021W (IRC25/POC3) and YPL144W (POC4) encode interacting proteins that function in proteasome assembly, with putative homologues widespread among eukaryotes. Several additional mutants suffered from defects in proteasome-mediated proteolysis. These included mutants in the urmylation pathway of protein modification (but not the Urm1 modifier itself) and the Reg1 regulatory subunit of protein phosphatase 1. Finally, we noted increased rates of ornithine decarboxylase turnover in an rpn10Delta mutant in which the degradation of certain ubiquitinated substrates is impaired. Together, these results highlight the utility of a ubiquitin-independent degron in uncovering novel factors affecting general and substrate-specific proteasome function.

Evidence-based behavioral interventions for repetitive behaviors in autism.

Restricted and repetitive behaviors (RRBs) are a core symptom of autism spectrum disorders (ASD). There has been an increased research emphasis on repetitive behaviors; however, this research primarily has focused on phenomenology and mechanisms. Thus, the knowledge base on interventions is lagging behind other areas of research. The literature suggests there are evidence-based practices to treat "lower order" RRBs in ASD (e.g., stereotypies); yet, there is a lack of a focused program of intervention research for "higher order" behaviors (e.g., insistence on sameness). This paper will (a) discuss barriers to intervention development for RRBs; (b) review evidence-based interventions to treat RRBs in ASD, with a focus on higher order behaviors; and (c) conclude with recommendations for practice and research.

Effects of a family-implemented treatment on the repetitive behaviors of children with autism.

The restricted and repetitive behaviors of children with autism can interfere with family functioning as well as learning and socialization opportunities for the child. To date, neither pharmacological nor comprehensive behavioral treatments have been found to be consistently effective at significantly reducing children's engagement in repetitive behaviors. We developed Family-Implemented Treatment for Behavioral Inflexibility (FITBI) to target the full variety of repetitive behaviors found in autism. For the current study, a therapist and parents of five children with autism (mean age = 48 months) co-implemented FITBI in a clinic setting over a 12-week treatment period. Using single case design methodology, significant reductions in repetitive behaviors were found for all participants and maintenance of treatment effects for 4 of 5 participants.

An easily dissociated 26 S proteasome catalyzes an essential ubiquitin-mediated protein degradation pathway in Trypanosoma brucei.

The 26 S proteasome, a complex between the 20 S proteasome and 19 S regulatory units, catalyzes ATP-dependent degradation of unfolded and ubiquitinated proteins in eukaryotes. We have identified previously 20 S and activated 20 S proteasomes in Trypanosoma brucei, but not 26 S proteasome. However, the presence of 26 S proteasome in T. brucei was suggested by the hydrolysis of casein by cell lysate, a process that requires ATP but is inhibited by lactacystin, and the lactacystin-sensitive turnover of ubiquitinated proteins in the intact cells. T. brucei cDNAs encoding the six proteasome ATPase homologues (Rpt) were cloned and expressed. Five of the six T. brucei Rpt cDNAs, except for Rpt2, were capable of functionally complementing the corresponding rpt deletion mutants of Saccharomyces cerevisiae. Immunoblots showed the presence in T. brucei lysate of the Rpt proteins, which co-fractionated with the yeast 19 S proteasome complex by gel filtration and localized in the 19 S fraction of a glycerol gradient. All the Rpt and putative 19 S non-ATPase (Rpn) proteins were co-immunoprecipitated from T. brucei lysate by individual anti-Rpt antibodies. Treatment of T. brucei cells with a chemical cross-linker resulted in co-immunoprecipitation of 20 S proteasome with all the Rpt and Rpn proteins that sedimented in a glycerol gradient to the position of 26 S proteasome. These data demonstrate the presence of 26 S proteasome in T. brucei cells, which apparently dissociate into 19 S and 20 S complexes upon cell lysis. RNA interference to block selectively the expression of proteasome 20 S core and Rpt subunits resulted in significant accumulation of ubiquitinated proteins accompanied by cessation of cell growth. Expression of yeast RPT2 gene in T. brucei Rpt2-deficient cells could not rescue the lethal phenotype, thus confirming the incompatibility between the two Rpt2s. The T. brucei 11 S regulator (PA26)-deficient RNA interference cells grew normally, suggesting the dispensability of activated 20 S proteasome in T. brucei.