Exposure to Microbial Metabolite Butyrate Prolongs the Survival Time and Changes the Growth Pattern of Human Papillomavirus 16 E6/E7-Immortalized Keratinocytes in Vivo.

Human papillomavirus (HPV) is a ubiquitous human pathogen that can be cleared by host immunity. Nonetheless, a small percentage of the patients develop persistent infection with oncogenic HPV, which poses an increased risk of developing HPV-associated malignancy. Although cell-mediated immunity is a known systemic factor, local factors that influence persistent HPV infection have not been fully investigated. HPV-related head/neck cancers have a strong site preference for the oropharynx, suggesting the existence of unique local factors that promote HPV-induced oncogenesis. The human oropharynx often harbors anaerobic bacteria that produce a variety of byproducts, including butyrate. Because butyrate is a potent epigenetic modulator, it could be an environmental factor influencing the development of HPV-positive oropharyngeal malignancy. In this study, we showed that butyrate treatment changed the property of HPV16 E6/E7-immortalized keratinocytes. In vitro, the treatment increased the cells' migration ability, slowed the growth, and increased the genotoxic resistance. When implanted in the syngeneic mice, the treated keratinocytes survived longer and exhibited a different growth pattern. The survival advantage obtained after butyrate exposure may increase the susceptibility of HPV-infected oropharyngeal keratinocytes to further malignant transformation. These results suggest that fermentation products of tonsillar bacteria may play an important role in the long-term persistence of high-risk HPV infection, which is a critical risk factor for developing HPV-positive oropharyngeal malignancy.

Achieving Inclusive Healthcare through Integrating Education and Research with AI and Personalized Curricula.

Precision medicine promises significant health benefits but faces challenges such as the need for complex data management and analytics, interdisciplinary collaboration, and education of researchers, healthcare professionals, and participants. Addressing these needs requires the integration of computational experts, engineers, designers, and healthcare professionals to develop user-friendly systems and shared terminologies. The widespread adoption of large language models (LLMs) like GPT-4 and Claude 3 highlights the importance of making complex data accessible to non-specialists. The Stanford Data Ocean (SDO) strives to mitigate these challenges through a scalable, cloud-based platform that supports data management for various data types, advanced research, and personalized learning in precision medicine. SDO provides AI tutors and AI-powered data visualization tools to enhance educational and research outcomes and make data analysis accessible for users from diverse educational backgrounds. By extending engagement and cutting-edge research capabilities globally, SDO particularly benefits economically disadvantaged and historically marginalized communities, fostering interdisciplinary biomedical research and bridging the gap between education and practical application in the biomedical field.

Increasing community capacity to reduce tobacco-related health disparities in African American communities.

OBJECTIVE: The purpose of this study was to understand the processes and interactions that African American tobacco control organizations use to engage African American communities in tobacco control efforts. DESIGN AND SAMPLE: The study used grounded theory methods to interpret participant's perspectives on tobacco control. The study sample consisted of African American tobacco control program directors from African American tobacco control organizations throughout the United States. MEASURES: Data collection involved 1 interview per participant using a semistructured interview at a location selected by the participant. Each interview lasted approximately 30-90 min. RESULTS: The results showed that organizations used specific strategies to involve African Americans in tobacco control. The tobacco control organizations built community capacity using 3 processes: developing relationships and partnerships, raising awareness, and creating collective power. CONCLUSION: Contextual, cultural processes, and historical references used by African American tobacco control organizations provide insight into how to engage African American communities in tobacco control efforts and achieve tobacco-related health parity. Public health professionals and nurses should be aware of these and other strategies that may increase the involvement of African American communities in tobacco control.

Molecular cytogenetic characterization of human papillomavirus16-transformed foreskin keratinocyte cell line 16-MT.

Anogenital cancers are closely associated with human papillomavirus (HPV), and HPV-infected individuals, particularly those with high-grade dysplasias, are at increased risk for cervical and anal cancers. Although genomic instability has been documented in HPV-infected keratinocytes, the full spectrum of genetic changes in HPV-associated lesions has not been fully defined. To address this, we examined an HPV16-transformed foreskin keratinocyte cell line, 16-MT, by GTG-banding, spectral karyotyping (SKY), and array comparative genomic hybridization (array CGH); these analyses revealed multiple numerical, complex, and cryptic chromosome rearrangements. Based on GTG-banding, the 16-MT karyotype was interpreted as 78-83,XXY,+add(1)(p36.3),+3,+4,+5,+5,+7,+8,+i(8)(q10)x2,+10,?der(12),der(13;14)(q10;q10),+15,+16,add(19)(q13.3),+21,+21,-22[cp20]. Multicolor analysis by SKY confirmed and further characterized the anomalies identified by GTG banding. The add(1) was identified as a der(1)(1qter-->1q25::1p36.1-->1qter), the add(19) as a dup(19), and the der(12) interpreted as a der(11) involving a duplication of chromosome 11 material and rearrangement with chromosome 19. In addition, previously unidentified der(9)t(9;22), der(3)t(3;19), and der(4)t(4;9) were noted. The 16-MT cell line showed losses and gains of DNA due to unbalanced translocations and complex rearrangements of regions containing known tumor suppressor genes. Chromosomal changes in these regions might explain the increased risk of cancer associated with HPV. Also, array CGH detected copy-number gains or amplifications of chromosomes 2, 8, 10, and 11 and deletions of chromosomes 3, 4, 11, and 15. These results provide the basis for the identification of candidate oncogenes responsible for cervical and anal cancer in amplified regions, and for putative tumor suppressor genes in commonly deleted regions like 11q22-23. Furthermore, these data represent the first full characterization of the HPV-positive cell line 16-MT.

The effectiveness of Web-based vs. non-Web-based interventions: a meta-analysis of behavioral change outcomes.

BACKGROUND: A primary focus of self-care interventions for chronic illness is the encouragement of an individual's behavior change necessitating knowledge sharing, education, and understanding of the condition. The use of the Internet to deliver Web-based interventions to patients is increasing rapidly. In a 7-year period (1996 to 2003), there was a 12-fold increase in MEDLINE citations for "Web-based therapies." The use and effectiveness of Web-based interventions to encourage an individual's change in behavior compared to non-Web-based interventions have not been substantially reviewed. OBJECTIVE: This meta-analysis was undertaken to provide further information on patient/client knowledge and behavioral change outcomes after Web-based interventions as compared to outcomes seen after implementation of non-Web-based interventions. METHODS: The MEDLINE, CINAHL, Cochrane Library, EMBASE, ERIC, and PSYCHInfo databases were searched for relevant citations between the years 1996 and 2003. Identified articles were retrieved, reviewed, and assessed according to established criteria for quality and inclusion/exclusion in the study. Twenty-two articles were deemed appropriate for the study and selected for analysis. Effect sizes were calculated to ascertain a standardized difference between the intervention (Web-based) and control (non-Web-based) groups by applying the appropriate meta-analytic technique. Homogeneity analysis, forest plot review, and sensitivity analyses were performed to ascertain the comparability of the studies. RESULTS: Aggregation of participant data revealed a total of 11,754 participants (5,841 women and 5,729 men). The average age of participants was 41.5 years. In those studies reporting attrition rates, the average drop out rate was 21% for both the intervention and control groups. For the five Web-based studies that reported usage statistics, time spent/session/person ranged from 4.5 to 45 minutes. Session logons/person/week ranged from 2.6 logons/person over 32 weeks to 1008 logons/person over 36 weeks. The intervention designs included one-time Web-participant health outcome studies compared to non-Web participant health outcomes, self-paced interventions, and longitudinal, repeated measure intervention studies. Longitudinal studies ranged from 3 weeks to 78 weeks in duration. The effect sizes for the studied outcomes ranged from -.01 to .75. Broad variability in the focus of the studied outcomes precluded the calculation of an overall effect size for the compared outcome variables in the Web-based compared to the non-Web-based interventions. Homogeneity statistic estimation also revealed widely differing study parameters (Q(w16) = 49.993, P < or = .001). There was no significant difference between study length and effect size. Sixteen of the 17 studied effect outcomes revealed improved knowledge and/or improved behavioral outcomes for participants using the Web-based interventions. Five studies provided group information to compare the validity of Web-based vs. non-Web-based instruments using one-time cross-sectional studies. These studies revealed effect sizes ranging from -.25 to +.29. Homogeneity statistic estimation again revealed widely differing study parameters (Q(w4) = 18.238, P < or = .001). CONCLUSIONS: The effect size comparisons in the use of Web-based interventions compared to non-Web-based interventions showed an improvement in outcomes for individuals using Web-based interventions to achieve the specified knowledge and/or behavior change for the studied outcome variables. These outcomes included increased exercise time, increased knowledge of nutritional status, increased knowledge of asthma treatment, increased participation in healthcare, slower health decline, improved body shape perception, and 18-month weight loss maintenance.

Additive effects of numbness and muscle aches on fatigue occurrence in individuals with HIV/AIDS who are taking antiretroviral therapy.

CONTEXT: Muscle aches, numbness in the feet/toes (neuropathy), and fatigue are often reported concurrently and are among the symptoms most frequently reported by individuals with HIV/AIDS, whether or not they are taking antiretroviral therapy (ART). OBJECTIVES: This study used a longitudinal analytical methodology to analyze these symptoms together to determine whether symptom clusters are maintained over time and to determine whether there is a temporal relationship between fatigue and reports of neuropathic pain and muscle aches. METHODS: This was a secondary analysis of a subset of data from a six-month, longitudinal, randomized, controlled trial of 243 HIV-positive individuals taking ART. Self-reported symptom frequency and intensity were recorded using the Revised Sign and Symptom Checklist for Persons with HIV disease at baseline (Month 0), one, three, and six months. Multilevel, logistic regression models were used to analyze time-lagged effects of muscle aches, numbness of the feet/toes, and fatigue to estimate any predictive and interactive effects that the symptoms have upon one another. RESULTS: A significant relationship between muscle aches and fatigue intercepts was noted (odds ratio [OR]=1.80, P≤0.05). Significant relationships between numbness and fatigue also were noted for the entire measurement period (OR=2.70, P≤0.05). Time-lagged models showed persons reporting neuropathic-related numbness in one period were nearly twice as likely to report fatigue in subsequent periods (OR=1.89, P≤0.05). The final model revealed that the addition of muscle aches and numbness explained 28% of the random variance in the occurrence of fatigue. Between-person descriptive variables including years living with HIV, age, having an AIDS diagnosis, ethnicity, and nucleoside reverse transcriptase inhibitor treatment regimens with stavudine, zalactabine, or didanosine did not significantly explain any additional model variation. CONCLUSION: These findings are consistent with physiological research and provide evidence that analyzing multiple symptom change over time can provide a more accurate representation of an individual's symptom experience. When evaluating patients with muscle aches or numbness, particularly when both symptoms are present, an evaluation of fatigue should be considered. Similarly, if fatigue is reported, underlying physiological assessments for neuropathic symptoms and muscle aches may be considered.