CRISPR-Cas9 is a system that it is not only revolutionary in expeditious sequencing of deoxyribonucleic acids (DNA) but also serves to induce genomic alterations within the sequence as well. The methodology that allows CRISPR to behave in such a manner is its ability to function in conjunction with ribonucleic acids (RNA). A facet of this RNA is its ability to scale from micro to macro organisms and by doing so, represents an observable deviation in its sequence. These sequential changes in RNA are observable in the form of protospacer adjacent motif (PAM) nucleotides which directly associate with the single guiding RNA (sgRNA) systems that direct DNA to the Cas9 enzyme. These PAM nucleotides are segments on RNA that are changed when DNA is altered and can be monitored. Cas9 is the protein component of CRISPR that is responsible for genome editing. However, the problem is that there hasn’t been conclusive evidence that demonstrates sgRNA will scale in complex genomes such as mice or humans. My objective is to observe how the PAM nucleotides behave in a multicellular Mammalia organism such as Mice to determine if RNA is directing DNA to the Cas9 enzyme and inducing genetic alterations. To observe these PAM nucleotides, the Mice genome will be subject to the introduction of Cas9 systems to be observed with PCR, gel electrophoresis, and Illumina sequencing. These are techniques that will yield data that signify if CRISPR is effective in altering mice genomes. With significant observable deviations in the PAM nucleotide sequences, the conclusion will be that CRISPR-Cas9 is able to induce alterations in complex genomes such as Mice and eventually humans.

Fungal infections are increasing in prevalence worldwide, especially in immunocompromised individuals. Given the emergence of drug-resistant fungi and the fact that there are only three major classes of antifungal drugs available to treat invasive fungal infections, there is a need to develop alternative therapeutic strategies effective against fungal infections. Candida albicans is a commensal of the human microbiota that is also one of the most common fungal pathogens isolated from clinical settings. C. albicans possesses several virulence traits that contribute to its pathogenicity, including the ability to form drug-resistant biofilms, which can make C. albicans infections particularly challenging to treat. Here, we explored red, green, and blue visible lights alone and in combination with common photosensitizing compounds for their efficacies at inhibiting and disrupting C. albicans biofilms. We found that blue light inhibited biofilm formation and disrupted mature biofilms on its own and that the addition of photosensitizing compounds improved its antibiofilm potential. Red and green lights, however, inhibited biofilm formation only in combination with photosensitizing compounds but had no effects on disrupting mature biofilms. Taken together, these results suggest that photodynamic therapy may be an effective non-drug treatment for fungal biofilm infections that is worthy of further exploration.

BACKGROUND: Despite the pivotal role of clinical trials in advancing orthopaedic oncology knowledge and treatment strategies, the persistent issues of trial discontinuation and nonpublication are significant problems. This study conducted an analysis examining clinical trial discontinuation rates, associations between intervention types and discontinuation/nonpublication, and the role of funding, enrollment size, and their implications for trial success and completion. METHODS: This study, conducted on May 1, 2023, utilized a cross-sectional design to comprehensively analyze phase 3 and 4 randomized controlled trials within the realm of orthopaedic oncology. We specifically incorporated Phase 3 and 4 trials as they are designed to evaluate prolonged outcomes in human subjects and are more likely to reach publication. Study characteristics of interest included the intervention utilized in the clinical trial, presence of funding, whether the trial was published, completed, and trial enrollment size. The investigation involved an examination of ClinicalTrials.gov, a prominent online repository of clinical trial data managed by the National Library of Medicine of the USA. Descriptive statistics and multivariate logistic regressions were used to determine statistical significance. RESULTS: Among the cohort of 130 trials, 19.2% were prematurely discontinued. Completion rates varied based on intervention type; 111 pharmaceutical trials demonstrated a completion rate of 83.8%, whereas 19 non-pharmaceutical trials exhibited a completion rate of 8.0% (P < .001). Surgical trials, totaling 10, showed a completion rate of 90%. The overall trial publication rate was 86.15%, with pharmaceutical interventions achieving a publication rate of 91.96%. Larger-scale trials (≥ 261 participants) emerged as a protective factor against both discontinuation (Adjusted Odds Ratio [AOR]: 0.85, 95% Confidence Interval [CI] 0.42-0.95) and nonpublication (AOR: 0.19, 95% CI 0.13-.47), compared to smaller-scale trials. CONCLUSION: This study accentuates the heightened vulnerability of non-pharmaceutical interventions and trials exhibiting lower rates of enrollment to the issues of discontinuation and nonpublication. Moving forward, the advancement of clinical trials necessitates a concerted effort to enhance trial methodologies, especially concerning nonpharmaceutical interventions, along with a meticulous refinement of participant enrollment criteria.

Introduction

Musculoskeletal (MSK) disease is a substantial global burden, especially in lower income countries. However, limited research has been published on MSK health by scholars from these countries. We aimed to study the distribution of authorships, including trends in peer-reviewed orthopaedic publications based on each author's affiliated institution's country income status.

Methods

Based on a bibliometric search, 119 orthopaedic-related journals were identified using the Journal Citation Reports database. Details of all scientific articles published in these journals between 2012 and 2021 were used to study trends and association between each of the author's affiliated institution's country income status, using the World Bank Classification.

Results

Of the 133,718 unique articles, 87.6% had at least one author affiliation from a high-income country (HIC), 7.0% from an upper-middle income country (UMIC), 5.2% from a lower-middle income country (LMIC), and 0.2% from a low-income country (LIC). Overall, these articles were cited 1,825,365 times, with 92.5% of citations from HIC-affiliated authors and < 0.1% from LIC-affiliated authors. Over the 10-year study period, HIC-affiliated articles demonstrated the largest increase in the number of publications (9107-14,619), compared to UMIC-affiliated (495-1214), LMIC-affiliated (406-874), and LIC-affiliated articles (4-28).

Conclusions

There are large and persistent disparities in orthopaedic research publications based on the country income status of the author's affiliated institution, especially in the higher impact orthopaedic journals. Efforts should be made to increase opportunities for scholars from LICs and LMICs to publish their research in high-impact orthopaedic journals.

Objective

To determine the prevalence and sociodemographic correlates of cyberbullying victimization and perpetration among a racially, ethnically and socioeconomically diverse population-based sample of 11-12-year-old early adolescents.

Methods

We analyzed cross-sectional data from the Adolescent Brain Cognitive Development (ABCD) Study (Year 2; N = 9429). Multiple logistic regression analyses were used to estimate associations between sociodemographic factors (sex, race/ethnicity, sexual orientation, country of birth, household income, parental education) and adolescent-reported cyberbullying victimization and perpetration.

Results

In the overall sample, lifetime prevalence of cyberbullying victimization was 9.6%, with 65.8% occurring in the past 12 months, while lifetime prevalence of cyberbullying perpetration was 1.1%, with 59.8% occurring in the past 12 months. Boys reported higher odds of cyberbullying perpetration (AOR 1.71, 95% CI 1.01-2.92) but lower odds of cyberbullying victimization (AOR 0.80, 95% CI 0.68-0.94) than girls. Sexual minorities reported 2.83 higher odds of cyberbullying victimization (95% CI 1.69-4.75) than nonsexual minorities. Lower household income was associated with 1.64 (95% CI 1.34-2.00) higher odds of cyberbullying victimization than higher household income, however household income was not associated with cyberbullying perpetration. Total screen time, particularly on the internet and social media, was associated with both cyberbullying victimization and perpetration.

Conclusions

Nearly one in 10 early adolescents reported cyberbullying victimization. Pediatricians, parents, teachers, and online platforms can provide education to support victims and prevent perpetration for early adolescents at the highest risk of cyberbullying.

Background

Problematic screen use, defined as an inability to control use despite private, social, and professional life consequences, is increasingly common among adolescents and can have significant mental and physical health consequences. Adverse Childhood Experiences (ACEs) are important risk factors in the development of addictive behaviors and may play an important role in the development of problematic screen use.

Methods

Prospective data from the Adolescent Brain Cognitive Development Study (Baseline and Year 2; 2018-2020; N = 9,673, participants who did not use screens were excluded) were analyzed in 2023. Generalized logistic mixed effects models were used to determine associations with ACEs and the presence of problematic use among adolescents who used screens based on cutoff scores. Secondary analyses used generalized linear mixed effects models to determine associations between ACEs and adolescent-reported problematic use scores of video games (Video Game Addiction Questionnaire), social media (Social Media Addiction Questionnaire), and mobile phones (Mobile Phone Involvement Questionnaire). Analyses were adjusted for potential confounders including age, sex, race/ethnicity, highest parent education, household income, adolescent anxiety, depression, and attention-deficit symptoms, study site, and participants who were twins.

Results

The 9,673 screen-using adolescents ages 11-12 years old (mean age 12.0) were racially and ethnically diverse (52.9% White, 17.4% Latino/Hispanic, 19.4% Black, 5.8% Asian, 3.7% Native American, 0.9% Other). Problematic screen use rates among adolescents were identified to be 7.0% (video game), 3.5% (social media), and 21.8% (mobile phone). ACEs were associated with higher problematic video game and mobile phone use in both unadjusted and adjusted models, though problematic social media use was associated with mobile screen use in the unadjusted model only. Adolescents exposed to 4 or more ACEs experienced 3.1 times higher odds of reported problematic video game use and 1.6 times higher odds of problematic mobile phone use compared to peers with no ACEs.

Conclusions

Given the significant associations between adolescent ACE exposure and rates of problematic video and mobile phone screen use among adolescents who use screens, public health programming for trauma-exposed youth should explore video game, social media, and mobile phone use among this population and implement interventions focused on supporting healthy digital habits.

Objective

To determine sociodemographic correlates of problematic screen use (social media, video games, mobile phones) among a racially/ethnically and socioeconomically diverse population-based sample of 10-14-year-old early adolescents.

Study design

We analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (Year 2, 2018-2020; N = 8753). Multiple linear regression analyses were used to estimate associations between sociodemographic factors (age, sex, race/ethnicity, primary language, household income, parental education) and adolescent-reported problematic video game (Video Game Addiction Questionnaire), social media (Social Media Addiction Questionnaire), and mobile phone use (Mobile Phone Involvement Questionnaire).

Results

Boys reported higher problematic video game use while girls reported higher problematic social media and mobile phone use. Native American, black, and Latinx adolescents reported higher scores across all problematic screen measures compared to non-Latinx white adolescents. Having unmarried/unpartnered parents was associated with higher problematic social media use. Although higher household income was generally protective against problematic video game use, these associations were weaker for black than white adolescents (p for interaction <0.05).

Conclusions

Given the sociodemographic differences in problematic screen use, digital literacy education strategies can focus on at-risk populations, encourage targeted counseling by pediatricians, and adapt family media use plans for diverse backgrounds.

Impact

While sociodemographic differences in screen time are documented, we examined sociodemographic differences in problematic screen use in a large, diverse sample of early adolescents in the US. Boys reported higher problematic video game use while girls reported higher problematic social media and mobile phone use. Native American, black, and Latinx adolescents reported higher scores across all problematic screen measures compared to non-Latinx white adolescents. Although higher household income was generally protective against problematic video game use, these associations were weaker for black than white adolescents. Beyond time spent on screens, pediatricians, parents, and educators should be aware of sociodemographic differences in problematic screen use.

Objective

To determine the association between cyberbullying (victimization and perpetration) and sleep disturbance among a demographically diverse sample of 10-14-year-old early adolescents.

Methods

We analyzed cross-sectional data from the Adolescent Brain Cognitive Development (ABCD) Study (Year 2, 2018-2020) of early adolescents (10-14 years) in the US. Modified Poisson regression analyses examined the association between cyberbullying and self-reported and caregiver-reported sleep disturbance measures.

Results

In a sample of 9,443 adolescents (mean age 12.0 years, 47.9% female, 47.8% white), 5.1% reported cyberbullying victimization, and 0.5% reported cyberbullying perpetration in the past 12 months. Cyberbullying victimization in the past 12 months was associated with adolescent-reported trouble falling/staying asleep (risk ratio [RR] 1.87, 95% confidence interval [CI] 1.57, 2.21) and caregiver-reported overall sleep disturbance of the adolescent (RR: 1.16 95% CI 1.00, 1.33), in models adjusting for sociodemographic factors and screen time. Cyberbullying perpetration in the past 12 months was associated with trouble falling/staying asleep (RR 1.95, 95% CI 1.21, 3.15) and caregiver-reported overall sleep disturbance of the adolescent (RR: 1.49, 95% CI 1.00, 2.22).

Conclusions

Cyberbullying victimization and perpetration are associated with sleep disturbance in early adolescence. Digital media education and counseling for adolescents, parents, teachers, and clinicians could focus on guidance to prevent cyberbullying and support healthy sleep behavior for early adolescents.

Objectives

To determine associations between bedtime screen time behaviors and sleep outcomes in a national study of early adolescents.

Methods

We analyzed cross-sectional data from 10,280 early adolescents aged 10-14 (48.8% female) in the Adolescent Brain Cognitive Development Study (Year 2, 2018-2020). Regression analyses examined the association between self-reported bedtime screen use and self- and caregiver-reported sleep measures, including sleep disturbance symptoms, controlling for sex, race/ethnicity, household income, parent education, depression, data collection period (pre- vs. during COVID-19 pandemic), and study site.

Results

Overall, 16% of adolescents had at least some trouble falling or staying asleep in the past 2 weeks and 28% had overall sleep disturbance, based on caregiver reports. Adolescents who had a television or an Internet-connected electronic device in the bedroom had a greater risk of having trouble falling or staying asleep (adjusted risk ratio 1.27, 95% CI 1.12-1.44) and overall sleep disturbance (adjusted risk ratio 1.15, 95% CI 1.06-1.25). Adolescents who left their phone ringer activated overnight had more trouble falling/staying asleep and greater overall sleep disturbance compared to those who turned off their cell phones at bedtime. Streaming movies, playing video games, listening to music, talking/texting on the phone, and using social media or chat rooms were all associated with trouble falling/staying asleep and sleep disturbance.

Conclusions

Several bedtime screen use behaviors are associated with sleep disturbances in early adolescents. The study's findings can inform guidance for specific bedtime screen behaviors among early adolescents.