Delineating Molecular Mechanisms of Squamous Tissue Homeostasis and Neoplasia: Focus on p63

Mouse models have informed us that p63 is critical for normal epidermal development and homeostasis. The p53/p63/p73 family is expressed as multiple protein isoforms due to a combination of alternative promoter usage and C-terminal alternative splicing. These isoforms can mimic or interfere with one another, and their balance ultimately determines biological outcome in a context-dependent manner. While not frequently mutated, p63, and in particular the ΔNp63 subclass, is commonly overexpressed in human squamous cell cancers. In vitro keratinocytes and murine transgenic and transplantation models have been invaluable in elucidating the contribution of altered p63 levels to cancer development, and studies have identified the roles for ΔNp63 isoforms in keratinocyte survival and malignant progression, likely due in part to their transcriptional regulatory function. These findings can be extended to human cancers; for example, the novel recognition of NFκB/c-Rel as a downstream effector of p63 has identified a role for NFκB/c-Rel in human squamous cell cancers. These models will be critical in enhancing the understanding of the specific molecular mechanisms of cancer development and progression

The Relationship Between Medical Diagnoses, Risk Perceptions, and Social Distancing Compliance: An Analysis of Data from the Toledo Adolescent Relationships Study

Background: The health belief model suggests that individuals' beliefs affect behaviors associated with health. This study examined whether Ohioans' pre-existing medical health diagnoses affected their belief about personal health risk and their compliance with social distancing during the coronavirus disease 2019 (COVID-19) pandemic. Prior research examining physical and mental diagnoses and social distancing compliance is nearly nonexistent. We examined whether physical and mental health diagnoses influenced individuals' beliefs that their health is at risk and their adherence with social distancing guidelines. Methods: The study used longitudinal cohort data from the Toledo Adolescent Relationships Study (TARS) (n = 790), which surveyed Ohioans prior to and during the COVID-19 pandemic. Dependent variables included belief that an individual's own health was at risk and social distancing compliance. Independent variables included physical and mental health diagnoses, pandemic-related factors (fear of COVID-19, political beliefs about the pandemic, friends social distance, family social distance, COVID-19 exposure), and sociodemographic variables (age, gender, race/ethnicity, educational level). Results: Individuals who had a pre-existing physical health diagnosis were more likely to believe that their personal health was at risk during the pandemic but were not more likely to comply with social distancing guidelines. In contrast, individuals who had a pre-existing mental health diagnosis were more compliant with social distancing guidelines but were not more likely to believe their personal health was at risk. Individuals who expressed greater fear of COVID-19 believed their health is more at risk than those who expressed lower levels of fear. Conclusion: Health considerations are important to account for in assessments of responses to the pandemic, beliefs about personal health risk, and social distancing behavior. Additional research is needed to understand the divergence in the findings regarding physical health, beliefs about personal health risk, and social distancing compliance. Further, research is needed to understand how mental health issues impact decision-making related to social distancing compliance

Development of ASMBS Research Agenda for Bariatric Surgery Using the Delphi Methodology

Background While the number of research publications related to bariatric surgery have increased remarkably in the past decade, research efforts remain uncoordinated and have limited focus, and numerous important questions remain unanswered. Objective To generate a research agenda in bariatric surgery. Setting National survey. Methods The membership of the American Society of Metabolic and Bariatric Surgery (ASMBS) was asked to submit research questions needed to advance the field of bariatric surgery. An expert panel grouped and collated submitted questions and redistributed them back to the membership to rate their importance on a 5-point Likert scale using a 3-round modified Delphi methodology. The top research questions were determined based on provided rankings. Results Two hundred ninety-two research questions were initially submitted that were collapsed to 59 unique questions. The ratings for the top 40 questions ranged from 2.67–4.33 (overall mean, 3.46). The highest-ranked questions centered on the mechanisms of effectiveness of bariatric surgery for weight loss and diabetes resolution, the underlying etiology of weight recidivism, and predictors of success. Conclusions A research agenda for bariatric surgery was developed using the Delphi methodology. This research agenda may enhance the ability of investigators and funding organizations, including the ASMBS, to focus attention to areas most likely to advance the field, and by editors and reviewers to assess the merit and relevance of scientific contributions

Prevalence and clinical features of patients with concurrent HBsAg and anti‐HBs: Evaluation of the hepatitis B research network cohort

The prevalence of concurrent HBsAg and anti‐HBs in plasma of persons with chronic hepatitis B virus (HBV) infection is variable and its clinical significance enigmatic. We examined the prevalence and clinical and virological features of concurrent HBsAg and anti‐HBs in children and adults with chronic HBV infection living in North America. A total of 1462 HBsAg positive participants in the Hepatitis B Research Network paediatric and adult cohorts were included (median age 41 (range 4‐80) years, 48% female, 11% white, 13% black, 73% Asians). Only 18 (1.2%) were found to be anti‐HBs positive (≥10 mIU/mL) at initial study evaluation. Distributions of sex, race, HBV genotype and ALT were similar between participants with and without concurrent anti‐HBs. Those who were anti‐HBs positive appeared to be older (median age 50 vs 41 years, P = .06), have lower platelet counts (median 197 vs 222 × 103/mm3, P = .07) and have higher prevalence of HBeAg (44% vs 26%, P = .10). They also had lower HBsAg levels (median 2.0 vs 3.5 log10 IU/mL, P = .02). Testing of follow‐up samples after a median of 4 years (range 1‐6) in 12 of the 18 participants with initial concurrent anti‐HBs showed anti‐HBs became undetectable in 6, decreased to <10 mIU/mL in 1 and remained positive in 5 participants. Two patients lost HBsAg during follow‐up. In conclusion, prevalence of concurrent HBsAg and anti‐HBs was low at 1.2%, with anti‐HBs disappearing in some during follow‐up, in this large cohort of racially diverse children and adults with chronic HBV infection living in North America. Presence of concurrent HBsAg and anti‐HBs did not identify a specific phenotype of chronic hepatitis B, nor did it appear to affect clinical outcomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156489/3/jvh13312.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156489/2/jvh13312-sup-0001-FigS1-S3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156489/1/jvh13312_am.pd

Malnutrition defined by GLIM criteria identifies a higher incidence of malnutrition and is associated with pulmonary complications after oesophagogastric cancer surgery, compared to ICD-10-defined malnutrition

Background & Objectives Low muscle mass, measured using computed tomography (CT), is associated with poor surgical outcomes. We aimed to include CT-muscle mass in malnutrition diagnosis using the Global Leadership Initiative on Malnutrition (GLIM) criteria, compare it to the International Classification of Diseases 10th Revision (ICD-10) criteria, and assess the impact on postoperative outcomes after oesophagogastric (OG) cancer surgery. Methods One hundred and eight patients who underwent radical OG cancer surgery and had preoperative abdominal CT imaging were included. GLIM and ICD-10 malnutrition data were assessed against complication and survival outcomes. Low CT-muscle mass was determined using predefined cut-points. Results GLIM-defined malnutrition prevalence was significantly higher than ICD-10-malnutrition (72.2% vs. 40.7%, p < 0.001). Of the 78 patients with GLIM-defined malnutrition, low muscle mass (84.6%) was the predominant phenotypic criterion. GLIM-defined malnutrition was associated with pneumonia (26.9% vs. 6.7%, p = 0.010) and pleural effusions (12.8% vs. 0%, p = 0.029). Postoperative complications did not correlate with ICD-10 malnutrition. Severe GLIM (HR: 2.51, p = 0.014) and ICD-10 (HR: 2.15, p = 0.039) malnutrition were independently associated with poorer 5-year survival. Conclusions GLIM criteria appear to identify more malnourished patients and more closely relate to surgical risk than ICD-10 malnutrition, likely due to incorporating objective muscle mass assessment

Objectively measured physical activity of USA adults by sex, age, and racial/ethnic groups: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Accelerometers were incorporated in the 2003–2004 National Health and Nutritional Examination Survey (NHANES) study cycle for objective assessment of physical activity. This is the first time that objective physical activity data are available on a nationally representative sample of U.S. residents. The use of accelerometers allows researchers to measure total physical activity, including light intensity and unstructured activities, which may be a better predictor of health outcomes than structured activity alone. The aim of this study was to examine objectively determined physical activity levels by sex, age and racial/ethnic groups in a national sample of U.S. adults.</p> <p>Methods</p> <p>Data were obtained from the 2003–2004 NHANES, a cross-sectional study of a complex, multistage probability sample of the U.S. population. Physical activity was assessed with the Actigraph AM-7164 accelerometer for seven days following an examination. 2,688 U.S. adults with valid accelerometer data (i.e. at least four days with at least 10 hours of wear-time) were included in the analysis. Mean daily total physical activity counts, as well as counts accumulated in minutes of light, and moderate-vigorous intensity physical activity are presented by sex across age and racial/ethnic groups. Generalized linear modeling using the log link function was performed to compare physical activity in sex and racial/ethnic groups adjusting for age.</p> <p>Results</p> <p>Physical activity decreases with age for both men and women across all racial/ethnic groups with men being more active than women, with the exception of Hispanic women. Hispanic women are more active at middle age (40–59 years) compared to younger or older age and not significantly less active than men in middle or older age groups (i.e. age 40–59 or age 60 and older). Hispanic men accumulate more total and light intensity physical activity counts than their white and black counterparts for all age groups.</p> <p>Conclusion</p> <p>Physical activity levels measured objectively by accelerometer demonstrated that Hispanic men are, in general, more active than their white and black counterparts. This appears to be in contrast to self-reported physical activity previously reported in the literature and identifies the need to use objective measures in situations where the contribution of light intensity and/or unstructured physical activity cannot be assumed homogenous across the populations of interest.</p

Ecological and Genomic Attributes of Novel Bacterial Taxa That Thrive in Subsurface Soil Horizons.

While most bacterial and archaeal taxa living in surface soils remain undescribed, this problem is exacerbated in deeper soils, owing to the unique oligotrophic conditions found in the subsurface. Additionally, previous studies of soil microbiomes have focused almost exclusively on surface soils, even though the microbes living in deeper soils also play critical roles in a wide range of biogeochemical processes. We examined soils collected from 20 distinct profiles across the United States to characterize the bacterial and archaeal communities that live in subsurface soils and to determine whether there are consistent changes in soil microbial communities with depth across a wide range of soil and environmental conditions. We found that bacterial and archaeal diversity generally decreased with depth, as did the degree of similarity of microbial communities to those found in surface horizons. We observed five phyla that consistently increased in relative abundance with depth across our soil profiles: Chloroflexi, Nitrospirae, Euryarchaeota, and candidate phyla GAL15 and Dormibacteraeota (formerly AD3). Leveraging the unusually high abundance of Dormibacteraeota at depth, we assembled genomes representative of this candidate phylum and identified traits that are likely to be beneficial in low-nutrient environments, including the synthesis and storage of carbohydrates, the potential to use carbon monoxide (CO) as a supplemental energy source, and the ability to form spores. Together these attributes likely allow members of the candidate phylum Dormibacteraeota to flourish in deeper soils and provide insight into the survival and growth strategies employed by the microbes that thrive in oligotrophic soil environments.IMPORTANCE Soil profiles are rarely homogeneous. Resource availability and microbial abundances typically decrease with soil depth, but microbes found in deeper horizons are still important components of terrestrial ecosystems. By studying 20 soil profiles across the United States, we documented consistent changes in soil bacterial and archaeal communities with depth. Deeper soils harbored communities distinct from those of the more commonly studied surface horizons. Most notably, we found that the candidate phylum Dormibacteraeota (formerly AD3) was often dominant in subsurface soils, and we used genomes from uncultivated members of this group to identify why these taxa are able to thrive in such resource-limited environments. Simply digging deeper into soil can reveal a surprising number of novel microbes with unique adaptations to oligotrophic subsurface conditions

Human immunodeficiency virus coinfection differentially impacts hepatitis B virus viral markers based on hepatitis Be antigen status in patients with suppressed viremia

Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg), reflecting transcriptional activity of covalently closed circular DNA, are gaining traction as important markers to assess viral activity. Whether their expression differs under viral suppression by HIV co-infection status is unknown. Among adults with chronic HBV on antiviral therapy, we sought to determine if the expression of HBV markers (specialized and well-established) differs between HBV-HIV co-infection vs. HBV mono-infection. We compared HBV marker levels among 105 participants in the Hepatitis B Research Network (HBRN) HBV-HIV Ancillary Study and 105 participants in the HBRN mono-infected Cohort Study, matched for HBeAg status and HBV DNA suppression on therapy. Among HBeAg+ participants (N = 58 per group), after adjusting for age, sex, race, ALT and HBV DNA, viral markers were higher (p &lt; .05) in the HBV-HIV versus the HBV-only sample (HBeAg: 1.05 vs. 0.51 log10 IU/mL; HBsAg: 3.85 vs. 3.17 log10 IU/mL; HBV RNA: 5.60 vs. 3.70 log10 U/mL; HBcrAg: 6.59 vs. 5.51 log10 U/mL). Conversely, among HBeAg(-) participants (N = 47 per group), HBsAg (2.00 vs. 3.04 log10 IU/mL) and HBV RNA (1.87 vs. 2.66 log10 U/mL) were lower (p &lt; .05) in HBV-HIV vs. HBV-only; HBcrAg levels were similar (4.14 vs. 3.64 log10 U/mL; p = .27). Among adults with chronic HBV with suppressed viremia on antiviral therapy, viral markers tracked with HIV co-infection status and associations differed inversely by HBeAg status. The greater sensitivity and specificity of HBV RNA compared to HBcrAg allows for better discrimination of transcriptional activity regardless of HBeAg status

Physical Activity Levels of Patients Undergoing Bariatric Surgery in the Longitudinal Assessment of Bariatric Surgery (LABS) Study

Background- Bariatric surgery candidates' physical activity (PA) level may contribute to the variability of weight loss and body composition changes following bariatric surgery. However, there is little research describing the PA of patients undergoing bariatric surgery to inform PA recommendations in preparation for, and following, surgery. Objectives- Describe PA assessment in the LABS-2 study and report pre-surgery PA level. Examine relationships between objectively determined PA level and 1) BMI and 2) self-reported purposeful exercise. Setting- Six sites in the U.S. Methods- Participants wore an accelerometer and completed a PA diary. Standardized measures of height and weight were obtained. Results- Of 757 participants, 20% were sedentary (<5000 steps/day), 34% low active (5000-7499 steps/day), 27% somewhat active (7500-9999 steps/day), 14% active (10000-12499 steps/day), and 6% were highly active (greater than or equal to 12500 steps/day). BMI was inversely related to mean steps/day and mean steps/minute during the most active 30 minutes each day. The most commonly reported activities were walking, 44%; gardening, 11%; playing with children, 10%; and stretching, 7%. Self-report of minutes of exercise accounted for 2% of the variance in objectively determined steps. Conclusion- Patients present for bariatric surgery with a wide range of PA levels, with almost half categorized as somewhat active or active. BMI is inversely related to total amount and intensity of PA. Few patients report a regular pre-operative exercise regimen suggesting most PA is accumulated from activities of daily living. Patient report of daily minutes of walking or exercise may not be a reliable indication of their PA level. Originally published Surgery for Obesity and Related Diseases, Vol. 4, No. 6, Nov-Dec 200

Sediment Cores from White Pond, South Carolina, contain a Platinum Anomaly, Pyrogenic Carbon Peak, and Coprophilous Spore Decline at 12.8 ka

A widespread platinum (Pt) anomaly was recently documented in Greenland ice and 11 North American sedimentary sequences at the onset of the Younger Dryas (YD) event (~12,800 cal yr BP), consistent with the YD Impact Hypothesis. We report high-resolution analyses of a 1-meter section of a lake core from White Pond, South Carolina, USA. After developing a Bayesian age-depth model that brackets the late Pleistocene through early Holocene, we analyzed and quantified the following: (1) Pt and palladium (Pd) abundance, (2) geochemistry of 58 elements, (3) coprophilous spores, (4) sedimentary organic matter (OC and sedaDNA), (5) stable isotopes of C (δ13C) and N (δ15N), (6) soot, (7) aciniform carbon, (8) cryptotephra, (9) mercury (Hg), and (10) magnetic susceptibility. We identified large Pt and Pt/Pd anomalies within a 2-cm section dated to the YD onset (12,785 ± 58 cal yr BP). These anomalies precede a decline in coprophilous spores and correlate with an abrupt peak in soot and C/OC ratios, indicative of large-scale regional biomass burning. We also observed a relatively large excursion in δ15N values, indicating rapid climatic and environmental/hydrological changes at the YD onset. Our results are consistent with the YD Impact Hypothesis and impact-related environmental and ecological changes