High sugar diet alters immune function and the gut microbiome in juvenile green iguanas (Iguana iguana).

The present work aimed to study whether a high sugar diet can alter immune responses and the gut microbiome in green iguanas. Thirty-six iguanas were split into four treatment groups using a 2×2 design. Iguanas received either a sugar-supplemented diet or a control diet, and either a lipopolysaccharide (LPS) injection or a phosphate-buffered saline (PBS) injection. Iguanas were given their respective diet treatment through the entire study (∼3 months) and received a primary immune challenge 1 and 2 months into the experiment. Blood samples and cloacal swabs were taken at various points in the experiment and used to measure changes in the immune system (bacterial killing ability, lysis and agglutination scores, LPS-specific IgY concentrations), and alterations in the gut microbiome. We found that a sugar diet reduces bacterial killing ability following an LPS challenge, and sugar and the immune challenge temporarily alters gut microbiome composition while reducing alpha diversity. Although sugar did not directly reduce lysis and agglutination following the immune challenge, the change in these scores over a 24-h period following an immune challenge was more drastic (it decreased) relative to the control diet group. Moreover, sugar increased constitutive agglutination outside of the immune challenges (i.e. pre-challenge levels). In this study, we provide evidence that a high sugar diet affects the immune system of green iguanas (in a disruptive manner) and alters the gut microbiome.

High risk features in colorectal adenomatous polyps: A multi-institutional study.

High risk features in colorectal adenomatous polyps include size >1 cm and advanced histology: high-grade dysplasia and villous architecture. We investigated whether the diagnostic rates of advanced histology in colorectal adenomatous polyps were similar among institutions across the United States, and if not, could differences be explained by patient age, polyp size, and/or CRC rate. Nine academic institutions contributed data from three pathologists who had signed out at least 100 colorectal adenomatous polyps each from 2018 to 2019 taken from patients undergoing screening colonoscopy. For each case, we recorded patient age and sex, polyp size and location, concurrent CRC, and presence or absence of HGD and villous features. A total of 2700 polyps from 1886 patients (mean age: 61 years) were collected. One hundred twenty-four (5 %) of the 2700 polyps had advanced histology, including 35 (1 %) with HGD and 101 (4 %) with villous features. The diagnostic rate of advanced histology varied by institution from 1.7 % to 9.3 % (median: 4.3 %, standard deviation [SD]: 2.5 %). The rate of HGD ranged from 0 % to 3.3 % (median: 1 %, SD: 1.2 %), while the rate of villous architecture varied from 1 % to 8 % (median: 3.7 %, SD: 2.5 %). In a multivariate analysis, the factor most strongly associated with advanced histology was polyp size >1 cm with an odds ratio (OR) of 31.82 (95 % confidence interval [CI]: 20.52-50.25, p < 0.05). Inter-institutional differences in the rate of polyps >1 cm likely explain some of the diagnostic variance, but pathologic subjectivity may be another contributing factor.

Genotype accounts for intraspecific variation in the timing and duration of multiple, sequential life-cycle events in a willow species.

PREMISE: Phenological variation among individuals within populations is common and has a variety of ecological and evolutionary consequences, including forming the basis for population-level responses to environmental change. Although the timing of life-cycle events has genetic underpinnings, whether intraspecific variation in the duration of life-cycle events reflects genetic differences among individuals is poorly understood. METHODS: We used a common garden experiment with 10 genotypes of Salix hookeriana (coastal willow) from northern California, United States to investigate the extent to which genetic variation explains intraspecific variation in the timing and duration of multiple, sequential life-cycle events: flowering, leaf budbreak, leaf expansion, fruiting, and fall leaf coloration. We used seven clones of each genotype, for a total of 70 individual trees. RESULTS: Genotype affected each sequential life-cycle event independently and explained on average 62% of the variation in the timing and duration of vegetative and reproductive life-cycle events. All events were significantly heritable. A single genotype tended to be "early" or "late" across life-cycle events, but for event durations, there was no consistent response within genotypes. CONCLUSIONS: This research demonstrates that genetic variation can be a major component underlying intraspecific variation in the timing and duration of life-cycle events. It is often assumed that the environment affects durations, but we show that genetic factors also play a role. Because the timing and duration of events are independent of one another, our results suggest that the effects of environmental change on one event will not necessarily cascade to subsequent events.

Prevalence of Nicotine and Tobacco Product Use by Sexual Identity, Gender Identity, and Sex Assigned at Birth Among Emerging Adult Tobacco Users in California, United States.

INTRODUCTION: Sexual and gender minority (SGM) nicotine and tobacco use disparities are well-documented among youth and young adults (YYA), and despite decades of prevention efforts, these disparities stubbornly persist. To better understand tobacco use disparities and craft tailored interventions, tobacco use patterns must be assessed in a contemporary sample of YYA across lines of sexual and gender identity, sex assigned at birth, and tobacco product types. AIMS AND METHODS: Data were from an online survey of a diverse sample of emerging adult tobacco users (ages 18-29; N = 1491) in California, United States (2020-2021). Participants were recruited from various online and in-person locations. Bivariate and adjusted models assessed differences in four nicotine and tobacco use outcomes (past 30-day use of cigarettes, e-cigarettes, other tobacco products, and multiple tobacco product types) across six groups: Cisgender heterosexual males, cisgender heterosexual females, cisgender sexual minority (SM) males, cisgender SM females, transfeminine participants, and transmasculine participants. RESULTS: Compared to cisgender heterosexual males, both transfeminine (OR = 2.25, 95% confidence intervals (CI) = 1.29 to 4.05) and transmasculine (OR = 1.85, 95% CI = 1.32 to 2.80) participants had higher odds of using cigarettes. Few differences were noted between groups in use of e-cigarettes. Cisgender heterosexual males had higher odds of other tobacco product use, compared to most other groups (eg, cisgender SM males: OR = 0.57, 95% CI = 0.37 to 0.87). Transmasculine participants had higher odds of multiple product use, compared to cisgender heterosexual females. Among multiple product users, transfeminine participants had the highest prevalence of using all three individual product types (35.6%). CONCLUSIONS: Results highlight the need for different tobacco control approaches across sexual and gender identities, sex assigned at birth, and nicotine and tobacco products. IMPLICATIONS: SGM nicotine and tobacco use disparities remain entrenched, despite concerted efforts to reduce them. The SGM population is heterogeneous and different SGM subgroups may have different needs. This study assessed, among young adult nicotine and tobacco users in California, U.S. patterns of tobacco use across sexual and gender identities, sex assigned at birth, as well as specific tobacco products used-a necessity to craft tailored tobacco control measures. We found patterns of nicotine and tobacco product use across several of these characteristics, highlighting how different prevention and cessation interventions may be needed to meaningfully address SGM nicotine and tobacco use disparities.

The associations between HIV stigma and mental health symptoms, life satisfaction, and quality of life among Black sexual minority men with HIV.

PURPOSE: With the advancement of antiretroviral therapy (ART), HIV/AIDS has become a manageable illness, similar to other chronic conditions. This study examined the associations between HIV stigma and patient-reported outcomes including mental health symptoms, life satisfaction, and quality of life among Black sexual minority men with HIV. METHODS: We analyzed baseline data from a randomized comparison trial of a mobile app intervention aimed to address the social work and legal needs of Black sexual minority men with HIV in Los Angeles County. We used validated scales including the Berger HIV stigma scale, the Patient Health Questionnaire-9 & the General Anxiety Disorder-7, the Satisfaction with Life Scale, and the Ladder Scale to assess HIV stigma, depressive symptoms, anxiety, life satisfaction, and quality of life, and we conducted multivariable linear regression to examine their associations. RESULTS: Participants experienced HIV stigma especially about disclosure concerns (e.g., 81.9% participants indicated "I am very careful who I tell that I have HIV") and public attitudes (52.3% believed "Most people with HIV are rejected when others find out"). In the multivariable models, higher overall stigma scores were associated with higher likelihood of experiencing depression (adjusted b = 0.235, p < 0.001) and anxiety (adjusted b = 0.188, p = 0.002), and lower life satisfaction (adjusted b = - 0.236, p < 0.001) and quality of life (adjusted b = - 0.053, p = 0.013), adjusting for clinical characteristics including ART initiation, viral load suppression, and medication adherence. In addition, being attacked or harassed in the past year were significantly associated with lower life satisfaction and quality of life (adjusted b = - 3.028, p = 0.046; adjusted b = - 1.438, p = 0.002). CONCLUSION: Our findings highlight the need for focused HIV stigma reduction interventions to promote the overall well-being of Black sexual minority men with HIV. Strategies to promote the patient-reported outcomes may benefit from trauma-informed approaches.

Outcomes of LGBTQ culturally sensitive training among civilian and military healthcare personnel.

BACKGROUND: Lesbian, gay, bisexual, transgender, or queer (LGBTQ) military servicemembers are at higher risk of developing health problems compared to heterosexual peers. To improve outcomes and address negative attitudes, previous literature has recommended education of healthcare personnel. The purpose of our study was to evaluate the knowledge and skill outcomes of an LGBTQ cultural sensitivity training program. METHODS: We used a pretest/posttest design. Participants completed the Ally Identity Measure (AIM) to assess three subscales: knowledge and skills, openness and support, and oppression awareness. Participants included both military and civilian healthcare personnel from multiple disciplines. Descriptive statistics and pairwise analyses were used. RESULTS: A total of 101 participants answered both pretest and posttest. Across all AIM subscales, posttest scores demonstrated statistically significant (P < 0.001) increases from mean pretest scores. Completion rates for the pretest and posttest were 99% and 93%, respectively. The majority of participants were female (75%) and non-Hispanic (87%), composed of Caucasians (39%) and Asians (33%). Over one-third (39%) of participants were aged 30-39. Fifty percent were active-duty military and more than half (58%) of all participants did not have prior training in LGBTQ patient care. Statistically significant differences were found between the pretest and posttest scores for the knowledge and skills subscale (M = 2.64-3.70). The most significant increases were observed in Item 12 and Item 15 (M = 2.72-3.70) regarding awareness of theories and skill development to provide proper support, respectively. CONCLUSION: These significant findings contribute to the currently limited research exploring LGBTQ cultural sensitivity training in both civilian and military settings. To our knowledge, this is the first time a cultural sensitivity training of this depth has been provided to active-duty servicemembers. Further research and development of similar educational programs integrating interactive participation can potentially aid in the delivery of improved care and military readiness for all servicemembers.

Somatic mutations in collagens are associated with a distinct tumor environment and overall survival in gastric cancer.

BACKGROUND: Gastric cancer is a heterogeneous disease with poorly understood genetic and microenvironmental factors. Mutations in collagen genes are associated with genetic diseases that compromise tissue integrity, but their role in tumor progression has not been extensively reported. Aberrant collagen expression has been long associated with malignant tumor growth, invasion, chemoresistance, and patient outcomes. We hypothesized that somatic mutations in collagens could functionally alter the tumor extracellular matrix. METHODS: We used publicly available datasets including The Tumor Cancer Genome Atlas (TCGA) to interrogate somatic mutations in collagens in stomach adenocarcinomas. To demonstrate that collagens were significantly mutated above background mutation rates, we used a moderated Kolmogorov-Smirnov test along with combination analysis with a bootstrap approach to define the background accounting for mutation rates. Association between mutations and clinicopathological features was evaluated by Fisher or chi-squared tests. Association with overall survival was assessed by Kaplan-Meier and the Cox-Proportional Hazards Model. Gene Set Enrichment Analysis was used to interrogate pathways. Immunohistochemistry and in situ hybridization tested expression of COL7A1 in stomach tumors. RESULTS: In stomach adenocarcinomas, we identified individual collagen genes and sets of collagen genes harboring somatic mutations at a high frequency compared to background in both microsatellite stable, and microsatellite instable tumors in TCGA. Many of the missense mutations resemble the same types of loss of function mutations in collagenopathies that disrupt tissue formation and destabilize cells providing guidance to interpret the somatic mutations. We identified combinations of somatic mutations in collagens associated with overall survival, with a distinctive tumor microenvironment marked by lower matrisome expression and immune cell signatures. Truncation mutations were strongly associated with improved outcomes suggesting that loss of expression of secreted collagens impact tumor progression and treatment response. Germline collagenopathy variants guided interpretation of impactful somatic mutations on tumors. CONCLUSIONS: These observations highlight that many collagens, expressed in non-physiologically relevant conditions in tumors, harbor impactful somatic mutations in tumors, suggesting new approaches for classification and therapy development in stomach cancer. In sum, these findings demonstrate how classification of tumors by collagen mutations identified strong links between specific genotypes and the tumor environment.

Social Determinants of Disease: HIV and COVID-19 Experiences.

PURPOSE OF REVIEW: The differential impact of the COVID-19 and HIV pandemics on marginalized communities has renewed calls for more robust and deeper investigation into structural and social causes of health inequities contributing to these infections, including underlying factors related to systematic racism. Using the Social Determinants of Health (SDOH) framework, we analyzed parallel and divergent factors associated with COVID-19 and HIV/AIDS and the prevalence of disparate disease in diverse communities. We utilized PRISMA guidelines to identify relevant literature (N = 210 articles) that resulted in a review of 125 articles included in our synthesis. RECENT FINDINGS: With racial health inequities as a core contributor to disease vulnerability, we also identified other factors such as economic stability, social and community support, the neighborhood and built environment, healthcare access and quality, and education access and quality as important socioecological considerations toward achieving health equity. Our review identifies structural and systematic factors that drive HIV and COVID-19 transmission. Our review highlights the importance of not solely focusing on biomedical interventions as solutions to ending HIV and COVID-19, but rather call for building a more just public health and social service safety net that meets the needs of people at the intersection of multiple vulnerabilities.

A Multi-institutional Study of Peritoneal Recurrence Following Resection of Low-grade Appendiceal Mucinous Neoplasms.

BACKGROUND: Peritoneal dissemination of low-grade appendiceal mucinous neoplasms (LAMNs), sometimes referred to as pseudomyxoma peritonei, can result in significant morbidity and mortality. Little is known about the natural history of localized (non-disseminated) LAMNs. OBJECTIVE: The goal of this study was to evaluate the risk of peritoneal recurrence in patients with localized LAMNs. METHODS: We performed a multi-institutional retrospective review of patients with pathologically confirmed localized LAMNs. Baseline characteristics, pathology, and follow-up data were collected. The primary endpoint was the rate of peritoneal recurrence. RESULTS: We identified 217 patients with localized LAMNs. Median age was 59 years (11-95) and 131 (60%) patients were female. Surgical management included appendectomy for 124 (57.1%) patients, appendectomy with partial cecectomy for 26 (12.0%) patients, and colectomy for 67 (30.9%) patients. Pathology revealed perforation in 46 patients (37.7% of 122 patients with perforation status mentioned in the report), extra-appendiceal acellular mucin (EAM) in 49 (22.6%) patients, and extra-appendiceal neoplastic cells (EAC) in 13 (6.0%) patients. Median follow-up was 51.1 months (0-271). Seven (3.2%) patients developed a peritoneal recurrence, with a median time to recurrence of 14.4 months (2.5-47.0). Seven (15.2%) patients with histologic evidence of perforation had recurrence, versus no patients (0%) without perforation (p < 0.001); five (10.2%) patients with EAM versus two (1.2%) patients without EAM (p = 0.007), and one (7.7%) patient with EAC versus six (2.9%) patients without EAC (p = 0.355) had recurrence. CONCLUSIONS: This multi-institutional study represents the largest reported series of patients with localized LAMNs. In the absence of perforation or extra-appendiceal mucin or cells, recurrence was extremely rare; however, patients with any of these pathologic findings require careful follow-up.

Leveraging Social Media Activity and Machine Learning for HIV and Substance Abuse Risk Assessment: Development and Validation Study.

BACKGROUND: Social media networks provide an abundance of diverse information that can be leveraged for data-driven applications across various social and physical sciences. One opportunity to utilize such data exists in the public health domain, where data collection is often constrained by organizational funding and limited user adoption. Furthermore, the efficacy of health interventions is often based on self-reported data, which are not always reliable. Health-promotion strategies for communities facing multiple vulnerabilities, such as men who have sex with men, can benefit from an automated system that not only determines health behavior risk but also suggests appropriate intervention targets. OBJECTIVE: This study aims to determine the value of leveraging social media messages to identify health risk behavior for men who have sex with men. METHODS: The Gay Social Networking Analysis Program was created as a preliminary framework for intelligent web-based health-promotion intervention. The program consisted of a data collection system that automatically gathered social media data, health questionnaires, and clinical results for sexually transmitted diseases and drug tests across 51 participants over 3 months. Machine learning techniques were utilized to assess the relationship between social media messages and participants' offline sexual health and substance use biological outcomes. The F1 score, a weighted average of precision and recall, was used to evaluate each algorithm. Natural language processing techniques were employed to create health behavior risk scores from participant messages. RESULTS: Offline HIV, amphetamine, and methamphetamine use were correctly identified using only social media data, with machine learning models obtaining F1 scores of 82.6%, 85.9%, and 85.3%, respectively. Additionally, constructed risk scores were found to be reasonably comparable to risk scores adapted from the Center for Disease Control. CONCLUSIONS: To our knowledge, our study is the first empirical evaluation of a social media-based public health intervention framework for men who have sex with men. We found that social media data were correlated with offline sexual health and substance use, verified through biological testing. The proof of concept and initial results validate that public health interventions can indeed use social media-based systems to successfully determine offline health risk behaviors. The findings demonstrate the promise of deploying a social media-based just-in-time adaptive intervention to target substance use and HIV risk behavior.

Smooth muscle tumors of the gastrointestinal tract: an analysis of prognostic features in 407 cases.

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P < 0.0001 for all features). Age, sex, and margin status were not significantly associated with progression (P = 0.23, 0.82, and 0.07, respectively). A risk assessment table was created based on tumor site, size, and mitotic count, and Kaplan-Meier plots of progression-free survival for each subgroup revealed progression-based tiers. Based on our findings, it appears that nonesophageal gastrointestinal smooth muscle tumors measuring >10 cm and/or showing ≥3 mitoses/5 mm2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.

A multifunctional AAV-CRISPR-Cas9 and its host response.

CRISPR-Cas9 delivery by adeno-associated virus (AAV) holds promise for gene therapy but faces critical barriers on account of its potential immunogenicity and limited payload capacity. Here, we demonstrate genome engineering in postnatal mice using AAV-split-Cas9, a multifunctional platform customizable for genome editing, transcriptional regulation, and other previously impracticable applications of AAV-CRISPR-Cas9. We identify crucial parameters that impact efficacy and clinical translation of our platform, including viral biodistribution, editing efficiencies in various organs, antigenicity, immunological reactions, and physiological outcomes. These results reveal that AAV-CRISPR-Cas9 evokes host responses with distinct cellular and molecular signatures, but unlike alternative delivery methods, does not induce extensive cellular damage in vivo. Our study provides a foundation for developing effective genome therapeutics.

Loss of SMAD4 protein expression in gastrointestinal and extra-gastrointestinal carcinomas.

AIMS: SMAD4 (DPC4) is a tumour suppressor gene that is dysregulated in various tumour types, particularly pancreaticobiliary and gastrointestinal carcinomas. Corresponding loss of protein expression has been reported in approximately 50% of pancreatic and 25% of colonic adenocarcinomas. In the evaluation of carcinoma of unknown primary site, immunohistochemical loss of SMAD4 expression is often used to suggest pancreaticobiliary origin, but there are limited data on the spectrum of SMAD4 expression in carcinomas of other sites. This study evaluates the frequency of SMAD4 loss in a large cohort of carcinomas from diverse anatomical sites. METHODS AND RESULTS: Immunohistochemistry for SMAD4 was performed on tissue microarrays or whole tissue sections of 1210 carcinomas from various organs: gastrointestinal tract, liver, pancreas/biliary tract, lung, breast, thyroid, kidney, ovary and uterus. Expression was considered lost when there was complete absence of staining in tumour cell nuclei, in the presence of intact staining in non-neoplastic cells. SMAD4 loss was seen in 58% of pancreatic adenocarcinomas, 27% of appendiceal adenocarcinomas, 19% of colorectal adenocarcinomas, 16% of cholangiocarcinomas, 10% of lung adenocarcinomas and <5% of oesophageal, breast, gastric and mucinous ovarian adenocarcinomas. All papillary thyroid, hepatocellular, non-mucinous ovarian, endometrial and renal cell carcinomas showed intact SMAD4 nuclear expression. CONCLUSION: In addition to pancreaticobiliary, appendiceal and colonic tumours, SMAD4 loss is also seen in a small subset of other carcinomas, specifically breast, lung, oesophageal and gastric adenocarcinomas, all of which are typically CK7-positive, similar to pancreaticobiliary carcinoma. Awareness of SMAD4 loss in these other carcinoma types is helpful in the evaluation of carcinomas of unknown or uncertain primary site.

Survey of Nonalcoholic Fatty Liver Disease Knowledge, Nutrition, and Physical Activity Patterns Among the General Public in Beijing, China.

BACKGROUND: Despite high prevalence of nonalcoholic fatty liver disease in China, understanding of the disease appears to be low. AIMS: We assessed the knowledge of NAFLD among the public in Beijing, China, as well as diet and physical activity patterns, which may provide information useful for NAFLD prevention and management. METHODS: We surveyed adult patients and family members in the Peking University Health Science Center (PUHSC) ultrasound clinic and office staff in Beijing, China. Participants provided demographic and medical history data. NAFLD-related knowledge and diet and physical activity were assessed. RESULTS: A total of 1296 participants at the PUHSC clinic (51% female, median age 35, 61% college-educated) and 494 participants in offices (61% female, median age 43, 74% college-educated) completed the survey. Response rate was 68.4% and 96.7%, respectively. In clinic and offices, 44% versus 48% were overweight/obese, 5% had a history of diabetes in both groups, and 14% versus 23% had a personal history of NAFLD. Median knowledge score was 15 out of 25 in clinic versus 16 in offices. 44.9% reported minimal physical activity. Factors associated with higher NAFLD knowledge scores (> 16) on multivariate analysis included college education or higher (OR 1.7, p = 0.01), family history of hyperlipidemia (OR 1.96, p < 0.001), and number of sugary drinks per week (OR 0.74, p = 0.006). No factors were significantly associated with physical activity levels. CONCLUSIONS: Adults in Beijing had low knowledge about NAFLD, and most were not physically active. Programs to increase public awareness of NAFLD and promote physical activity are critical to curb this growing epidemic.

Risk Assessment of Hepatocellular Carcinoma in Patients with Hepatitis C in China and the USA.

BACKGROUND: Hepatitis C (HCV) infection is an increasingly common cause of hepatocellular carcinoma (HCC) in China. AIMS: We aimed to determine differences in demographic and behavioral profiles associated with HCC in HCV+ patients in China and the USA. METHODS: Consecutive HCV+ patients were recruited from centers in China and the USA. Clinical data and lifestyle profiles were obtained through standardized questionnaires. Multivariable analysis was conducted to determine factors associated with HCC diagnosis within groups. RESULTS: We included 41 HCC patients from China and 71 from the USA, and 931 non-HCC patients in China and 859 in China. Chinese patients with HCC were significantly younger, less likely to be male and to be obese than US patients with HCC (all p < 0.001). Chinese patients with HCC had a significantly lower rate of cirrhosis diagnosis (36.6 vs. 78.9%, p < 0.001); however, they also had a higher rate of hepatitis B core antibody positivity (63.4 vs. 36.8%, p = 0.007). In a multivariable analysis of the entire Chinese cohort, age > 55, male sex, the presence of diabetes, and time from maximum weight were associated with HCC, while tea consumption was associated with a decreased HCC risk (OR 0.37, 95% CI 0.16-0.88). In the US cohort, age > 55, male sex, and cirrhosis were associated with HCC on multivariable analysis. CONCLUSIONS: With the aging Chinese population and increasing rates of diabetes, there will likely be continued increase in the incidence of HCV-related HCC in China. The protective effect of tea consumption on HCC development deserves further validation.

Temporal Changes in the Modes of Hepatitis C Virus Transmission in the USA and Northern China.

BACKGROUND: Predominant modes of hepatitis C virus (HCV) transmission vary between countries and over time. AIMS: To compare HCV transmission modes in the USA and northern China. METHODS: We conducted a prospective study enrolling two cohorts of chronic HCV patients in the USA, and in China at Beijing, and at Gu'an and Kuancheng counties in Hebei. Patients self-reported the most likely source and year of infection. RESULTS: A total of 1957 patients were studied (1000 USA; 957 China-428 Beijing, 387 Gu'an, 142 Kuancheng). The predominant infection sources were transfusion (23.0%) and injection drug use (IDU) (32.1%) in the USA and transfusion (64.5%) in northern China. Within China, transfusion was the most common source in Beijing (62.1%) and Gu'an (88.1%), and medical procedures (35.9%) and IDU (12.0%) in Kuancheng. Infection via transfusion decreased significantly in the USA (35.1-4.6%) and Beijing (84.2-14.3%) but remained frequent in Gu'an (90.5-72.5%) over time. Infection via IDU decreased from 32.4% in those ≥61 years to 25.0% in those 41-50 years but increased to 46.5% in those ≤40 years in US patients and decreased over time from 38.7 to 1.9% in Kuancheng. Infection via medical procedures increased over time in Beijing (7.0-33.3%) and remained frequent in Kuancheng (45.2-31.1%). CONCLUSIONS: There are major differences in presumed HCV infection source between the USA and northern China. Favorable as well as worrisome changes in the modes of HCV transmission in both countries were observed.

Survey of hepatitis B knowledge and stigma among chronically infected patients and uninfected persons in Beijing, China.

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection carries substantial stigma in China. We surveyed HBV knowledge and stigma among chronic hepatitis B (CHB) patients and persons without HBV infection in Beijing, China. METHODS: Four hundred and thirty five CHB patients and 801 controls at Peking University People's Hospital were surveyed. RESULTS: Chronic hepatitis B patients were older (mean 46 vs. 39 years) and more often men (71 vs. 48%) than controls. Mean knowledge score was 11.9/15 for CHB and 9.3/15 for control patients (P < 0.001). Average stigma score was 22.1/39 for CHB and 19.2/30 for control patients. Controls expressed discomfort with close contact (45%) or sharing meals with CHB patients (39%) and believed CHB patients should not be allowed to work in restaurants (58%) or childcare (44%). Chronic hepatitis B patients felt that they were undesirable as spouses (33 vs. 17%) and brought trouble to their families (58 vs. 34%) more often than controls. Despite legal prohibitions, 40% of CHB patients were required to undergo pre-employment HBV testing, and 29% of these individuals thought that they lost job opportunities because of their disease status. 16% of CHB patients regretted disclosing their HBV status and disclosure was inversely associated with stigma. Higher stigma was associated with older age, lower education and lower knowledge score among controls; and with lower education, younger age, having undergone pre-employment HBV testing and regret disclosing their HBV status among CHB patients. CONCLUSION: Despite high prevalence of CHB in China, our study shows knowledge is limited and there is significant societal and internalized stigma associated with HBV infection.

A Comparative Study of Liver Disease Care in the USA and Urban and Rural China.

BACKGROUND: Chronic liver disease is a major cause of morbidity and mortality in the USA and China, but the etiology of liver disease, medical practice, and patient expectations in these two countries are different. AIMS: To compare patient knowledge about their liver disease, patient satisfaction with liver disease care, and patient medical decision-making preference in the USA and China. METHODS: Three cohorts of established adult patients with liver disease seen in liver clinics in Ann Arbor, USA, and Beijing (urban) and Hebei (rural), China, completed a survey between May and September 2014. RESULTS: A total of 990 patients (395 USA, 398 Beijing, and 197 Hebei) were analyzed. Mean liver disease knowledge score (maximum 5) in the USA, Beijing, and Hebei patients was 4.1, 3.6, and 3.0, respectively (p < 0.001). US patients had a greater preference for collaborative decision-making: 71.8 % preferred to make treatment decisions together with the doctor, while most Chinese patients (74.6 % Beijing and 84.8 % Hebei) preferred passive decision-making. Mean satisfaction score (maximum 85) in the USA was higher than in Beijing, which in turn was higher than in Hebei (78.2 vs. 66.5 vs. 60.3, p < 0.001). There was a positive correlation between liver disease knowledge score and satisfaction score (r = 0.27, p < 0.001) and with collaborative medical decision-making (r = 0.22, p < 0.001) when responses from all sites were combined. CONCLUSIONS: Liver disease knowledge and patient satisfaction were greatest in the USA, followed by Beijing and then Hebei patients. Understanding these differences and associated factors may help to improve patient outcomes.

Impact of Hydrocolloid Dressing and Moisturizing Cream as Facial Skin Protectants Among Health Care Workers.

INTRODUCTION: During the novel coronavirus disease 2019 pandemic, health care workers experienced facial problems from prolonged use of N95 masks, including skin irritation, pigmentation changes, and contact dermatitis. We assessed the use of hydrocolloid dressing versus dimethicone cream to prevent skin breakdown among military health care workers while wearing an N95. MATERIALS AND METHODS: Participants were recruited using convenience and snowball sampling in this nonblinded, randomized, cross-over study with 2 active treatments, hydrocolloid dressing and dimethicone cream, across 3 time points. The skin was assessed using photographs and subepidermal moisture scanner (SEM). N95 seal integrity was assessed using qualitative fit test. Institutional review board approval was obtained from the Madigan Army Medical Center Institutional Review Board. RESULTS: Among the 73 participants, wearing an N95 alone versus with dimethicone cream or hydrocolloid dressing caused more adverse skin reactions. There were no significant differences in qualitative fit test failure rate between groups. Participants experienced minimal to no dizziness, loss of energy/tiredness/fatigue, claustrophobia, shortness of breath, difficulty breathing, and dry or itchy eyes. For all interventions, wearing an N95 did not interfere with participants' concentration, verbal communication, hearing, vision, and, importantly, delivery of care. CONCLUSIONS: Using a skin protectant with an N95 may prevent adverse skin reactions while preserving health care workers' ability to safely and competently care for patients in routine and pandemic conditions.

Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses.

Selenoprotein K (Sel K) is a selenium-containing protein for which no function has been identified. We found that Sel K is an endoplasmic reticulum transmembrane protein expressed at relatively high levels in immune cells and is regulated by dietary selenium. Sel K(-/-) mice were generated and found to be similar to wild-type controls regarding growth and fertility. Immune system development was not affected by Sel K deletion, but specific immune cell defects were found in Sel K(-/-) mice. Receptor-mediated Ca(2+) flux was decreased in T cells, neutrophils, and macrophages from Sel K(-/-) mice compared with controls. Ca(2+)-dependent functions including T cell proliferation, T cell and neutrophil migration, and Fcγ receptor-mediated oxidative burst in macrophages were decreased in cells from Sel K(-/-) mice compared with that in cells from controls. West Nile virus infections were performed, and Sel K(-/-) mice exhibited decreased viral clearance in the periphery and increased viral titers in brain. Furthermore, West Nile virus-infected Sel K(-/-) mice demonstrated significantly lower survival (2 of 23; 8.7%) compared with that of wild-type controls (10 of 26; 38.5%). These results establish Sel K as an endoplasmic reticulum-membrane protein important for promoting effective Ca(2+) flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses.