Extreme Elevation of Baseline Intraoperative Parathyroid Hormone Measurements: Should Usual Protocols Apply?

INTRODUCTION: Intraoperative parathyroid hormone (IOPTH) monitoring is routinely used to facilitate minimally invasive parathyroidectomy. Many IOPTH protocols exist for predicting biochemical cure. Some patients are found to have extremely high baseline IOPTH levels (defined in this study as >500 pg/mL), which may affect the likelihood of satisfying certain final IOPTH criteria. We aimed to discover whether clinically significant differences exist in patients with extremely high baseline IOPTH and which IOPTH protocols are most appropriately applied to these patients. MATERIALS AND METHODS: This is a retrospective review of 237 patients who underwent parathyroidectomy with IOPTH monitoring for primary hyperparathyroidism (pHPT) from 2016 to 2020. Baseline IOPTH levels, drawn prior to manipulation of parathyroid glands, were grouped into categories labeled "elevated" (>65-500 pg/mL) and "extremely elevated" (>500 pg/mL). Final IOPTH levels were analyzed to determine whether there was a >50% decrease from baseline and whether a normal IOPTH value was achieved. 6-wk postoperative calcium levels were also examined. RESULTS: Of the patients in this cohort, 76% were in the elevated group and 24% in the extremely elevated group. Male sex and higher preoperative PTH levels were correlated with higher baseline IOPTH levels. Patients with extremely elevated baseline IOPTH were less likely to have IOPTH fall into normal range at the conclusion of the case (P = 0.019), and final IOPTH levels were higher (P < 0.001), but the IOPTH was equally likely to decrease >50% from baseline. There was no difference in the mean postoperative calcium levels between the two groups at 6-wk or at longer term follow-up (mean 525 d). CONCLUSIONS: Detection of baseline IOPTH levels >500 pg/mL during parathyroidectomy performed for pHPT is not uncommon. IOPTH in patients with extremely elevated baseline levels were less likely to fall into normal range, but follow-up calcium levels were equal, suggesting that applying more stringent IOPTH criteria for predicting biochemical cure may not be appropriate for this population.

The AICD fragment of APP initiates a FoxO3a mediated response via FANCD2.

The amyloid precursor protein (APP) is a cell surface protein of uncertain function that is notable for being the parent protein of beta-amyloid. Research around this protein has focussed heavily on the link to Alzheimer's disease and neurodegeneration. However, there is increasing evidence that APP may be linked to neuronal loss through mechanisms independent of beta-amyloid. FoxO3a is a transcription factor associated with neuronal longevity and apoptosis. In neurons, FoxO3a is associated with cell death through pathways that include BIM, a BCL-2 family member. In this study we have shown that APP overexpression increased the cellular levels and activity of FoxO3a. This increased expression and activity is not a result of decreased phosphorylation but is more likely a result of increased nuclear stability due to increased levels of FANCD2, a binding partner of FoxO3a. The changes caused by APP overexpression were shown to be due to the AICD fragment of APP possibly directly inducing transcription increase in FANCD2. These findings strengthen the link between APP metabolism and FoxO3a neuronal activity. This link may be crucial in better understanding the cellular role of APP and its link to neurodegeneration and aging.

From Practice to Publication: The Promise of Writing Workshops.

Practitioners in health departments, university extension programs, and nonprofit organizations working in public health face varied challenges to publishing in the peer-reviewed literature. These practitioners may lack time, support, skills, and efficacy needed for manuscript submission, which keeps them from sharing their wisdom and experience-based evidence. This exclusion can contribute to literature gaps, a failure of evidence-based practice to inform future research, reduced ability to educate partners, and delays in advancing public health practice. Our article describes the writing workshops offered to Division of Nutrition, Physical Activity, and Obesity (DNPAO), Centers for Disease Control and Prevention (CDC) funded programs in 2021. This project consisted of three 60-minute introductory writing webinars open to all recipients, followed by a Writing for Publications workshop, an 8- to 9-week virtual learning/writing intensive for selected writing team applicants. The Society for Public Health Education staff, consultants, and CDC/DNPAO staff developed, refined, and presented the curriculum. The workshop for public health practitioner writing teams was offered to two cohorts and included extensive coaching and focused on potential submission to a Health Promotion Practice supplement, "Reducing Chronic Disease through Physical Activity and Nutrition: Public Health Practice in the Field" (see Supplemental Material), which was supported by CDC/DNPAO. We describe the webinars, the workshop design, modifications, evaluation methods and results.

Built Environment Approaches to Increase Physical Activity: A Science Advisory From the American Heart Association.

Engaging in regular physical activity is one of the most important things people can do to improve their cardiovascular health; however, population levels of physical activity remain low in the United States. Effective population-based approaches implemented in communities can help increase physical activity among all Americans. Evidence suggests that built environment interventions offer one such approach. These interventions aim to create or modify community environmental characteristics to make physical activity easier or more accessible for all people in the places where they live. In 2016, the Community Preventive Services Task Force released a recommendation for built environment approaches to increase physical activity. This recommendation is based on a systematic review of 90 studies (search period, 1980-June 2014) conducted using methods outlined by the Guide to Community Preventive Services. The Community Preventive Services Task Force found sufficient evidence of effectiveness to recommend combined built environment strategies. Specifically, these strategies combine interventions to improve pedestrian or bicycle transportation systems with interventions to improve land use and environmental design. Components of transportation systems can include street pattern design and connectivity, pedestrian infrastructure, bicycle infrastructure, and public transit infrastructure and access. Components of land use and environmental design can include mixed land use, increased residential density, proximity to community or neighborhood destinations, and parks and recreational facility access. Implementing this Community Preventive Services Task Force recommendation in communities across the United States can help promote healthy and active living, increase physical activity, and ultimately improve cardiovascular health.

U.S. Older Adults' Participation in Balance Activities.

The Physical Activity Guidelines for Americans, second edition recommends that older adults do multicomponent physical activity, which includes balance training in addition to aerobic and muscle-strengthening activities. The authors estimated the prevalence of U.S. older adults (age ≥65 years) who do balance activities and meet the aerobic and muscle-strengthening physical activity guidelines. The authors analyzed data on 1,012 respondents to the 2019 FallStyles survey, a nationwide web-based panel survey. Approximately four in 10 respondents (40.7%) reported doing balance activities on ≥1 day/week, 34.0% on ≥2 days/week, and 25.3% on ≥3 days/week. Prevalence differed by sex, education level, income level, census region, body mass index category, and meeting the aerobic and/or muscle-strengthening guidelines. The combined prevalence of participation in balance activities and meeting aerobic and muscle-strengthening guidelines ranged from 12.0% for ≥3 days/week to 15.8% for ≥1 day/week. Opportunities exist to introduce and increase participation in balance and multicomponent activities by older adults.

Senescent Microglia: The Key to the Ageing Brain?

Ageing represents the single biggest risk factor for development of neurodegenerative disease. Despite being such long-lived cells, microglia have been relatively understudied for their role in the ageing process. Reliably identifying aged microglia has proven challenging, not least due to the diversity of cell populations, and the limitations of available models, further complicated by differences between human and rodent cells. Consequently, the literature contains multiple descriptions and categorisations of microglia with neurotoxic phenotypes, including senescence, without any unifying markers. The role of microglia in brain homeostasis, particularly iron storage and metabolism, may provide a key to reliable identification.

Cross-sectional association between physical activity level and subjective cognitive decline among US adults aged ≥45 years, 2015.

Subjective cognitive decline (SCD) is the self-reported experience of worsening or more frequent confusion or memory loss within the previous 12 months and can be one of the earliest symptoms of Alzheimer's disease. Regular physical activity can contribute to the primary, secondary, and tertiary prevention of cognitive decline. At the national level, prevalence estimates of SCD by physical activity level in the United States are currently unknown. The purpose of this study is to examine the prevalence of SCD and resulting functional limitations by physical activity level among US adults aged ≥45 years. Data from 33 states and the District of Columbia participating in the 2015 Behavioral Risk Factor Surveillance System (N = 128,925) were analyzed. We estimated the prevalence of SCD (a positive response to a question about worsening or more frequent confusion or memory loss within the previous 12 months) and resulting functional limitations overall and by self-reported physical activity level based on current guidelines (i.e., active, insufficiently active, and inactive). Odds ratios were estimated using logistic regression models adjusting for respondent characteristics. Overall, 11.3% of US adults aged ≥45 years reported SCD. Prevalence of SCD increased as physical activity level decreased (active: 8.8%; insufficiently active: 11.4%; inactive: 15.7%). Among those with SCD, the prevalence of functional limitations also increased as physical activity level decreased (active: 40.5%; insufficiently active: 50.0%; inactive: 57.4%). These differences largely remained after adjusting for respondent characteristics. Findings highlight the potential public health impact nationally of efforts to promote physical activity for cognitive health.

Microglia and the aging brain: are senescent microglia the key to neurodegeneration?

The single largest risk factor for etiology of neurodegenerative diseases like Alzheimer's disease is increased age. Therefore, understanding the changes that occur as a result of aging is central to any possible prevention or cure for such conditions. Microglia, the resident brain glial population most associated with both protection of neurons in health and their destruction is disease, could be a significant player in age related changes. Microglia can adopt an aberrant phenotype sometimes referred to either as dystrophic or senescent. While aged microglia have been frequently identified in neurodegenerative diseases such as Alzheimer's disease, there is no conclusive evidence that proves a causal role. This has been hampered by a lack of models of aged microglia. We have recently generated a model of senescent microglia based on the observation that all dystrophic microglia show iron overload. Iron-overloading cultured microglia causes them to take on a senescent phenotype and can cause changes in models of neurodegeneration similar to those observed in patients. This review considers how this model could be used to determine the role of senescent microglia in neurodegenerative diseases.

Levels of α- and ß-synuclein regulate cellular susceptibility to toxicity from α-synuclein oligomers.

α-Synuclein (α-syn) is associated with a range of diseases, including Parkinson disease. In disease, α-syn is known to aggregate and has the potential to be neurotoxic. The association between copper and α-syn results in the formation of stellate toxic oligomers that are highly toxic to cultured neurons. We further investigated the mechanism of toxicity of α-syn oligomers. Cells that overexpress α-syn showed increased susceptibility to the toxicity of the oligomers, while those that overexpressed ß-syn showed increased resistance to the toxic oligomers. Elevated α-syn expression caused an increase in expression of the transcription factor Forkhead box O3a (FoxO3a). Inhibition of FoxO3a activity by the overexpression of DNA binding domain of FoxO3a resulted in significant protection from α-syn oligomer toxicity. Increased FoxO3a expression in cells was shown to be caused by increased ferrireductase activity and Fe(II) levels. These results suggest that α-syn increases FoxO3a expression as a result of its intrinsic ferrireductase activity. The results also suggest that FoxO3a plays a pivotal role in the toxicity of both Fe(II) and toxic α-syn species to neuronal cells.-Angelova, D. M., Jones, H. B. L., Brown, D. R. Levels of α- and ß-synuclein regulate cellular susceptibility to toxicity from α-synuclein oligomers.

Assessing exposure to unconventional natural gas development: using an air pollution dispersal screening model to predict new-onset respiratory symptoms.

Various exposure estimates have been used to assess health impact of unconventional natural gas development (UNGD). The purpose of this study was to (1) use an air pollution dispersal screening model and wind direction to characterize the air emissions from UNGD facilities at each residence and (2) assess association of this exposure estimate with respiratory symptoms. Respiratory symptoms were abstracted from health records of a convenience sample of 104 adults from one county in southwestern PA who had completed a standard clinical interview with a nurse practitioner. Using publicly available air emission data, we applied a "box" air pollution dispersion screening model to estimate the median ambient air level of CO, NOx, PM 2.5, VOCs, and formaldehyde at the residence during the year health symptoms were reported. Sources and median emissions were categorized as north, south, east, or west of the residence to account for the effect of wind direction on dispersion. Binary logistic regression was performed for each respiratory symptom. Number of sources had varying magnitudes of association with some symptoms (i.e., cough, shortness of breath, and "any respiratory symptom") and no association with others (i.e., sore throat, sinus problems, wheezing). Air emissions were not associated with any symptom.

Importance of the RpoE Regulon in Maintaining the Lipid Bilayer during Antimicrobial Treatment with the Polycationic Agent, Chlorhexidine.

The emergence of multidrug resistance in bacteria has reached alarming levels. To solve this growing problem, discovery of novel cellular targets or pathways important for antimicrobial resistance is urgently needed. In this study, we explored how the alternative sigma factor, RpoE, protects Escherichia coli O157 against the toxic effects of the polycationic antimicrobial agent, chlorhexidine (CHX). Susceptibility of this organism to CHX was found to directly correlate to the growth rate, with the faster replicating wild-type being more susceptible to CHX than its more slowly replicating ΔrpoE O157 mutant. Once the wild-type and rpoE mutant strains had undergone growth arrest (entered the stationary growth phase), their resistance to CHX became entirely dependent on the functionality of RpoE. The RpoE regulon plays a critical role in maintaining the integrity of the asymmetric lipid bilayer of E. coli, thereby preventing the intracellular accumulation of CHX. Finally, using a single-cell, high-resolution, synchrotron-based approach, we discovered a subpopulation of the rpoE mutant strain with no detectable intracellular CHX, a predominant characteristic of the wild-type CHX-resistant population. This finding reveals a role of phenotypic heterogeneity in antimicrobial resistance.

Prevalence of master plans supportive of active living in US municipalities.

Community planning documents can play an important role in promoting the design and maintenance of walkable communities. This study estimates the prevalence among US municipalities of (1) community wide planning documents and (2) inclusion of plan objectives supportive of active living within these documents. Data from the 2014 National Survey of Community-Based Policy and Environmental Supports for Healthy Eating and Active Living (CBS HEAL), a survey of local officials, were analyzed (n = 2005). Prevalence of comprehensive or general plans, 3 specific plan types, and 3 objectives supportive of active living were analyzed using survey weights to create national estimates. Overall, 64% of municipalities had a comprehensive/general plan, 46% had a transportation plan, 48% had a bicycle or pedestrian plan and 76% had a land use plan. Of municipalities with a plan, 78% included at least one of the three objectives measured supportive of active living. Differences in presence of plans and objectives were observed by population size of the municipality, urban status, region, and median education. Helping communities, especially smaller or rural municipalities and those with lower median education levels, create and adopt planning documents supportive of active living may be an important step in creating more walkable communities.

Racial and ethnic differences in perceived safety barriers to walking, United States National Health Interview Survey - 2015.

Barriers to safe walking may prevent people from being physically active, and previous reports have identified differences in barriers to safe walking across racial and ethnic groups. The purpose of this research was to determine the role demographic characteristics play on racial/ethnic differences in perceived barriers to safe walking and determine if racial/ethnic differences vary by urban/rural residence and Census region. Participants in the 2015 National Health Interview Survey Cancer Control Supplement (n = 31,433 adults ≥18 years) reported perceived barriers to safe walking (traffic, crime, and animals) and demographic characteristics. Urban/rural residence and Census region were based on home addresses. We calculated adjusted prevalence of barriers by race/ethnicity using logistic regression; geographic differences in barriers across racial/ethnic groups were examined via interaction terms. After adjustment for demographic characteristics, non-Hispanic blacks (blacks) and Hispanics reported crime and animals as barriers more frequently than non-Hispanic whites (whites) (crime: blacks, 22.2%; Hispanics, 16.7%; whites, 9.0%; animals: blacks, 18.0%; Hispanics, 12.4%; whites, 8.5%). Racial/ethnic differences in perceived crime as a barrier were more pronounced in the Northeast and Midwest than in the South and West. Urban-dwelling blacks (all regions) and Hispanics (Midwest and South) reported animals as barriers more frequently than whites. Racial/ethnic differences in perceived barriers to safe walking remained after adjusting for demographic characteristics and varied by geographic location. Addressing perceived crime and animals as barriers to walking could help reduce racial/ethnic differences in physical activity, and several barriers may need to be assessed to account for geographic variation.

Alpha-synuclein ferrireductase activity is detectible in vivo, is altered in Parkinson's disease and increases the neurotoxicity of DOPAL.

The normal cellular role of α-synuclein is of potential importance in understanding diseases in which an aggregated form of the protein has been implicated. A potential loss or change in the normal function of α-synuclein could play a role in the aetiology of diseases such as Parkinson's disease. Recently, it has been suggested that α-synuclein could cause the enzymatic reduction of iron and a cellular increase in Fe(II) levels. Experiments were carried out to determine if such activity could be measured in vivo. Experiments with rats overexpressing human α-synuclein in nigral dopaminergic neurons demonstrated a correlation between α-synuclein expression and ferrireductase activity. Furthermore, studies on tissue from Parkinson's disease patient brains showed a significant decrease in ferrireductase activity, possibly due to deposition of large amounts of inactive protein. Cellular studies suggest that increase ferrireductase activity results in increased levels of dopamine metabolites and increased sensitivity to the toxicity of DOPAL. These findings demonstrate that α-synuclein ferrireductase activity is present in vivo and its alteration may play a role in neuron loss in disease.

Symposium review: Microbial endocrinology-Why the integration of microbes, epithelial cells, and neurochemical signals in the digestive tract matters to ruminant health.

The union of microbiology and neurobiology, which has been termed microbial endocrinology, is defined as the study of the ability of microorganisms to produce and respond to neurochemicals that originate either within the microorganisms themselves or within the host they inhabit. It serves as the basis for an evolutionarily derived method of communication between a host and its microbiota. Mechanisms elucidated by microbial endocrinology give new insight into the ways the microbiota can affect host stress, metabolic efficiency, resistance to disease, and other factors that may prove relevant to the dairy industry.

Proportion of Adults Who Identified Walking As a US Surgeon General Priority.

In September 2015, Step It Up! The Surgeon General's Call to Action to Promote Walking and Walkable Communities (Call to Action) was released. This descriptive study reports the proportion of adults who responded to the 2016 Summer ConsumerStyles survey (N = 4,114) who identified walking as the activity the US Surgeon General recently promoted in the Call to Action to help Americans be more physically active. Less than half of adults (44%) correctly identified walking. Adults who were aged 18 to 24 years (35%), were male (43%), were non-Hispanic white (42%), or were physically inactive (36%) were less likely to identify walking than their counterparts. This study highlights an opportunity to raise awareness and promote the Call to Action, especially among certain populations.

Steady-State Kinetics of α-Synuclein Ferrireductase Activity Identifies the Catalytically Competent Species.

α-Synuclein (α-syn) is a cytosolic protein known for its association with neurodegenerative diseases, including Parkinson's disease and other synucleinopathies. The potential cellular function of α-synuclein may be of consequence for understanding the pathogenesis of such diseases. Previous work has suggested that α-synuclein can catalyze the reduction of iron as a ferrireductase. We performed a detailed analysis of the steady-state kinetics of recombinant α-syn ferrireductase activity and for disease-associated variants. Our study illustrates that the ferrireductase activity we observed is clearly commensurate with bona fide enzyme activity and suggests a mechanistic rationale for the activity and the relationship to cellular regulation of the pool of Fe(III) and Fe(II). Using cell-based studies, we examined the functionally active conformation and found that the major catalytically active form is a putative membrane-associated tetramer. Using an artificial membrane environment with recombinant protein, we demonstrate that secondary structure folding of α-synuclein is insufficient to allow enzyme activity and the absolute specificity of the tertiary/quaternary structure is the primary requirement. Finally, we explored the steady-state kinetics of a range of disease α-synuclein variants and found that variants involved in neurodegenerative disease exhibited major changes in their enzymatic activity. We discuss these data in the context of a potential disease-associated mechanism for aberrant α-synuclein ferrireductase activity.

Building Community: Stakeholder Perspectives on Walking in Malls and Other Venues.

Mall walking has been a popular physical activity for decades. However, little is known about why mall managers support these programs or why adults choose to walk. Our study aim was to describe mall walking programs from the perspectives of walkers, managers, and leaders. Twenty-eight walkers, 16 walking program managers, and six walking program leaders from five states participated in a telephone or in-person semi-structured interview (N = 50). Interview guides were developed using a social-ecological model. Interviews were recorded, transcribed verbatim, and analyzed thematically. All informants indicated satisfaction with their program and environmental features. Differences in expectations were noted in that walkers wanted a safe, clean, and social place whereas managers and leaders felt a need to provide programmatic features. Given the favorable walking environments in malls, there is an opportunity for public health professionals, health care organizations, and providers of aging services to partner with malls to promote walking.