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The rates of early-onset colorectal cancer (EO-CRC) have been rising by 0.5% to 2.4% annually for three decades, accounting for an estimated 12% of all colorectal cancer diagnosed in the United States in 2020. Enhancing the rigor and comprehensiveness of the epidemiology in terms of the exposures and prognostic biomarkers is essential if we are to modify risk factors and underlying mechanisms, ultimately arresting this unduly trend. This commentary serves to describe the disease trend, postulate underlying risk factors and mechanisms driving disease incidence, and proposes a call to action for cancer epidemiologists to promote increased and timely opportunities to intervene on this trend.

Vitamin D deficiency and insufficiency are associated with serious sequelae in childhood cancer survivors. However, data on vitamin D deficiency in children with newly diagnosed cancer are scarce and the role of sociodemographic factors and vitamin D supplementation is largely unknown. We assessed vitamin D status and its socio-demographic and clinical correlates in 163 children with newly diagnosed cancer, using 25-hydroxy vitamin D (25(OH)D) concentrations and assessed longitudinal changes following vitamin D supplementation. Sixty-five percent of the patients with newly diagnosed cancer had low 25(OH)D concentrations. Fifty-two patients (32%) were vitamin D deficient (≤20 ng/mL 25(OH)D concentration), and 53(33%) were insufficient (21-29 ng/mL 25(OH)D concentration). Age over 10 (P = 0.019), Hispanic ethnicity (P = 0.002), and female sex (P = 0.008) were significantly associated with lower 25(OH)D concentration at diagnosis. Vitamin D supplementation resulted in significant increase in 25(OH)D concentrations (P

Amid internationalizing shifts in higher education, universities around the world are simultaneously becoming more integrated and more disparate. This paper examines the role of immigration policy in producing convergent and divergent educational attainment among international and domestic students at Indian and US universities and shows that student and work visas influence international students' decisions about where to study, what to study, and how much education to pursue. Using original data sources and a transnational data collection strategy, this study develops new approaches to measuring international student mobility and offers a window into transnational phenomena not easily observable in other datasets. An analysis of 7177 education histories and 105 in-depth interviews with international students, university administrators, and immigration lawyers shows that migration policy contributes to the growth of international student enrollment and multinational educations but also creates asymmetrical student flows and funnels international students into certain fields of study. The results of this study indicate that migration policies simultaneously contribute to integration and differentiation between the US and Indian university systems. The findings show that immigration policies play an important role in regulating the flow and nature of international student migration streams and lead to simultaneous convergence and divergence in the educational attainment and field of study between Indian international students enrolled in US universities and their domestically educated peers in India. Through an empirical case, this paper develops a conceptual bridge between two dominant frameworks on internationalization and theorizes the central role of migration policy in shaping processes of higher education internationalization.

BackgroundSkin and soft tissue infections (SSTIs) are a key antimicrobial stewardship target because they are a common infection in hospitalized patients, and non-guideline-concordant antibiotic use is frequent. To inform antimicrobial stewardship interventions, we evaluated the proportion of veterans hospitalized with SSTIs who received guideline-concordant empiric antibiotics or an appropriate total duration of antibiotics.MethodsA retrospective medication use evaluation was performed in 34 Veterans Affairs Medical Centers between 2016 and 2017. Hospitalized patients who received antibiotics for uncomplicated SSTI were included. Exclusion criteria were complicated SSTI, severe immunosuppression, and antibiotics for any non-SSTI indication. Data were collected by manual chart review. The primary outcome was the proportion of patients receiving both guideline-concordant empiric antibiotics and appropriate treatment duration, defined as 5-10 days of antibiotics. Data were analyzed and reported using descriptive statistics.ResultsOf the 3890 patients manually evaluated for inclusion, 1828 patients met inclusion criteria. There were 1299 nonpurulent (71%) and 529 purulent SSTIs (29%). Overall, 250 patients (14%) received guideline-concordant empiric therapy and an appropriate duration. The most common reason for non-guideline-concordance was receipt of antibiotics targeting methicillin-resistant Staphylococcus aureus (MRSA) in 906 patients (70%) with a nonpurulent SSTI. Additionally, 819 patients (45%) received broad-spectrum Gram-negative coverage, and 860 patients (48%) received an antibiotic duration >10 days.ConclusionsWe identified 3 common opportunities to improve antibiotic use for patients hospitalized with uncomplicated SSTIs: use of anti-MRSA antibiotics in patients with nonpurulent SSTIs, use of broad-spectrum Gram-negative antibiotics, and prolonged durations of therapy.

BackgroundFiber-based prebiotic supplements are marketed for maintaining bowel health and promoting beneficial gut bacteria. However, the association between prebiotic supplement use and colorectal cancer risk and mortality is unknown.MethodsThe association between prebiotic use and colorectal cancer risk and mortality was evaluated in postmenopausal women in the Women's Health Initiative study. Self-reported prebiotic use was documented at study enrollment. Adjudicated colorectal cancer cases and mortality were captured using medical and death records. Cox proportional hazards models were used to estimate the HR related to prebiotic use and colorectal cancer risk and mortality.ResultsIn total, 3,032 colorectal cancer cases were diagnosed during an average 15.4 years of follow-up. Overall, 3.7% of women used a prebiotic with psyllium, the major fiber type. Use of any prebiotic supplement was not associated with colorectal cancer risk or mortality. The type of prebiotic supplement (none vs. insoluble or soluble) was not associated with colorectal cancer risk; however, use of insoluble fiber prebiotics compared with none was associated with higher colorectal cancer mortality [HR, 2.79; 95% confidence interval (CI), 1.32-5.90; P = 0.007]. Likelihood ratio tests indicated no significant interactions between prebiotic use and other colorectal cancer risk factors, including metabolic syndrome.ConclusionsPrebiotic fiber supplement use was not associated with colorectal cancer risk. Insoluble, but not soluble, prebiotic fiber use was associated with higher colorectal cancer mortality. These findings do not support the promotion of prebiotic fiber supplements to reduce colorectal cancer risk or colorectal cancer mortality.ImpactFurther investigation is warranted for findings regarding insoluble prebiotic fiber and higher colorectal cancer mortality in postmenopausal women.

This paper revisits conventional wisdom on US degree premiums for immigrant workers and shows that, despite the benefits of a US degree, migration policies and substandard labor conditions contribute to international student motivations to return home. Using two original datasets, I find that about a third of Indian-born US graduates leave the US, seeking employment opportunities abroad and a respite from US work visa restrictions. I draw on 105 in-depth interviews and 7,177 employment histories constructed from LinkedIn, and the analysis demonstrates the use of digital data to shed new light on under-studied patterns of return migration in institutional perspective. I find that US work visas are related to the underemployment of immigrant workers, and gaps in visa availability are associated with US labor market departure for Indian international students. At the same time, foreign employers reward skills and credentials developed in the US, and the results suggest that US degrees carry a higher premium in foreign labor markets. The paper emphasizes the role of institutions in the skilled migration system and identifies disjunctures in US migration policy. I identify opportunities for policy reform to improve immigrant labor conditions and increase the retention of US-educated migrants in the US labor market. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic not only disproportionately impacted the health of immigrants in the US, but led to financial disparities as well. However, few studies to date capture the experience of asylum-seeking and refugee populations. Methods: We analyzed semi-structured interviews conducted in fall 2021 with immigrants (primarily asylum-seekers and refugees from countries in Central and East Africa) and key informants, and conducted focus group discussions in spring 2023 with employees of a non-profit supporting the financial needs of asylum-seekers and refugees in Portland, ME. Results: We identified several ways in which the COVID-19 pandemic negatively impacted the financial stability of asylum-seekers and refugees, including: job loss, work permit backlog, lack of sick leave benefits, childcare expenses and related job strain, rising cost of basic goods, issues of housing availability/affordability, and healthcare expenses. Conclusion: Policy changes that address structural factors and support financial stability among asylum-seekers and refugees and other low-income populations could help mitigate the impact of future public health crises and ultimately improve health equity. [ABSTRACT FROM AUTHOR]

Adherence to the American Cancer Society's (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines is associated with reductions in overall cancer incidence and mortality, including site-specific cancers such as colorectal cancer. We examined the relationship between baseline adherence to the ACS guidelines and (1) baseline adenoma characteristics and (2) odds of recurrent colorectal adenomas over 3 years of follow-up. Cross-sectional and prospective analyses with a pooled sample of participants from the Wheat Bran Fiber (n = 503) and Ursodeoxycholic Acid (n = 854) trials were performed. A cumulative adherence score was constructed using baseline self-reported data regarding body size, diet, physical activity and alcohol consumption. Multivariable logistic regression demonstrated significantly reduced odds of having three or more adenomas at baseline for moderately adherent (odds ratio [OR] = 0.67, 95% confidence intervals [CI]: 0.46⁻0.99) and highly adherent (OR = 0.50, 95% CI: 0.31⁻0.81) participants compared to low adherers (p-trend = 0.005). Conversely, guideline adherence was not associated with development of recurrent colorectal adenoma (moderate adherence OR = 1.16, 95% CI: 0.85⁻1.59, high adherence OR = 1.23, 95% CI: 0.85⁻1.79).

DNA-based therapeutics have emerged as a revolutionary approach for addressing the treatment gap in rare inherited conditions by targeting the fundamental genetic causes of disease. Charcot–Marie–Tooth (CMT) disease, a group of inherited neuropathies, represents one of the most prevalent Mendelian disease groups in neurology and is characterized by diverse genetic aetiology. Axonal forms of CMT, known as CMT2, are caused by dominant mutations in >30 different genes that lead to degeneration of lower motor neuron axons. Recent advances in antisense oligonucleotide therapeutics have shown promise in targeting neurodegenerative disorders. Here, we elucidate pathomechanistic changes contributing to variant specific molecular phenotypes in CMT2E, caused by a single nucleotide substitution (p.N98S) in the neurofilament light chain gene (NEFL). We used a patient-derived induced pluripotent stem cell-induced motor neuron model that recapitulates several cellular and biomarker phenotypes associated with CMT2E. Using an antisense oligonucleotide treatment strategy targeting a heterozygous gain-of-function variant, we aimed to resolve molecular phenotypic changes observed in the CMT2E p.N98S subtype. To determine the therapeutic potential of antisense oligonucleotide, we applied our treatment strategy in induced pluripotent stem cell-derived motor neurons and used both established and new biomarkers of peripheral nervous system axonal degeneration. Our findings demonstrated a significant decrease in clinically relevant biomarkers of axonal degeneration, presenting the first clinically viable genetic therapeutic for CMT2E. Similar strategies could be used to develop precision medicine approaches for otherwise untreatable gain-of-function inherited disorders. [ABSTRACT FROM AUTHOR]

Pain and knee stiffness are common problems following total knee replacement surgery, with 10–20% of patients reporting dissatisfaction following their procedure. A remote assessment of knee stiffness could improve outcomes through continuous monitoring, facilitating timely intervention. Using machine learning algorithms, computer vision can extract joint angles from video footage, offering a method to monitor knee range of motion in patients' homes. This study outlines a protocol to provide proof of concept and validate a computer vision-based approach for measuring knee range of motion in individuals who have undergone total knee replacement. The study also explores the feasibility of integrating this technology into clinical practice, enhancing post-operative care. The study is divided into three components: carrying out focus groups, validating the computer vision-based software, and home testing. The focus groups will involve five people who underwent total knee replacement and ten healthcare professionals or carers who will discuss the deployment of the software in clinical settings. For the validation phase, 60 participants, including 30 patients who underwent total knee replacement surgery five to nine weeks prior and 30 healthy controls, will be recruited. The participants will perform five tasks, including the sit-to-stand test, where knee range of motion will be measured using computer vision-based markerless motion capture software, marker-based motion capture, and physiotherapy assessments. The accuracy and reliability of the software will be evaluated against these established methods. Participants will perform the sit-to-stand task at home. This will allow for a comparison between home-recorded and lab-based data. The findings from this study have the potential to significantly enhance the monitoring of knee stiffness following total knee replacement. By providing accurate, remote measurements and enabling the early detection of issues, this technology could facilitate timely referrals to non-surgical treatments, ultimately reducing the need for costly and invasive procedures to improve knee range of motion. [ABSTRACT FROM AUTHOR]

Background Emerging cancer treatments are often most available to socially advantaged individuals. This study examines the relationship of patient educational attainment, income level, and rurality to the receipt of genome-matched treatment and overall survival. Methods Survey and clinical data were collected from patients with cancer (n = 1258) enrolled in the Maine Cancer Genomics Initiative. Logistic regression models examined whether receipt of genome-matched treatment differed by patient education, income, and rurality. Kaplan–Meier curves and Cox regression were conducted to evaluate 12-month mortality. We completed additional exploratory analyses using Kaplan–Meier curves and Cox models stratified by receipt of genome-matched treatment. Logistic and Cox regression models were adjusted for age and gender. Results Educational attainment, income level, and rurality were not associated with genome-matched treatment receipt. Of 1258 patients, 462 (36.7%) died within 365 days of consent. Mortality risk was associated with lower educational attainment (hazard ratio [HR] = 1.30, 95% confidence interval [CI] = 1.06 to 1.59; P = .013). No statistically significant differences in mortality risk were observed for income level or rurality. Exploratory models suggest that patients who did not receive genome-matched treatment with lower educational attainment had higher mortality risk (HR = 1.36, 95% CI = 1.09 to 1.69; P = .006). For patients who did receive genome-matched treatment, there was no difference in mortality risk between the education groups (HR = 1.01, 95% CI = 0.56 to 1.81; P  > .9). Conclusion Although there were no disparities in who received genome-matched treatment, we found a disparity in mortality associated with education level, which was more pronounced for patients who did not receive genome-matched treatment. Future research is warranted to investigate the intersectionality of social disadvantage with clinical outcomes to address survival disparities. [ABSTRACT FROM AUTHOR]

Author(s): Natalie Guerrero [sup.1] [sup.2] , Ronald Gangnon [sup.1] , Marah A. Curtis [sup.3] , Carmen R. Valdez [sup.4] , Deborah B. Ehrenthal [sup.5] , Elizabeth A. Jacobs [sup.6] Author [...], Introduction We examined the association of exposure to maternal depression during year 2 of a child's life with future child problem behavior. We conducted a secondary analysis to investigate whether race/ethnicity is a moderator of this relationship. Methods We used Fragile Families and Child Well-Being Study data (age 3 N = 3288 and 49% Black, 26% Hispanic, 22% non-Hispanic White; age 5 N = 3001 and 51% Black, 25% Hispanic, 21% non-Hispanic White; age 9 N = 3630 and 50% Black, 25% Hispanic, 21% non-Hispanic White) and ordinal logistic regression to model problem behavior at ages 3, 5, and 9 on maternal depression status during year 2. Results At age 9, children whose mother was depressed during year 2 were significantly more likely to have higher internalizing (AOR = 1.92, 95% CI: 1.42,2.61) and externalizing (AOR = 1.65, 95% CI: 1.10,2.48) problem behavior scores. In our secondary analysis, race/ethnicity did not have moderating effects, potentially due to a limitation of the data that required use of maternal self-reported race/ethnicity as a proxy for child race/ethnicity. Discussion Exposure to maternal depression after the prenatal and perinatal periods may have a negative association with children's behavioral development through age 9. Interventions that directly target maternal depression during this time should be developed. Additional research is needed to further elucidate the role of race/ethnicity in the relationship between maternal depression and child problem behavior.

ObjectiveFor individuals with 1-2 small (

Selenium supplementation may help to prevent colorectal cancer; as precursors of colorectal cancer, colorectal adenomas are a surrogate for colorectal cancer. Selenium supplementation may increase risk of type 2 diabetes (T2D). The Selenium and Celecoxib (Sel/Cel) Trial was a randomized, placebo controlled trial of selenium 200 µg daily as selenized yeast and celecoxib 400 mg once daily, alone or together, for colorectal adenoma prevention. Men and women between age 40 and 80 years were eligible following colonoscopic removal of colorectal adenomas. The primary outcome was adenoma development. Celecoxib was suspended because of cardiovascular toxicity in other trials, but accrual continued to selenium and placebo. A total of 1621 participants were randomly assigned to selenium or placebo, of whom 1374 (84.8%) were available for analysis. All statistical tests were two-sided. In the respective placebo and selenium arms of 689 and 685 participants, adenoma detection after medians of 33.6 (range = 0.0-85.1 months) and 33.0 months (range = 0.0-82.6 months) were 42.8% and 44.1% (relative risk [RR] = 1.03, 95% confidence interval [CI] = 0.91 to 1.16, P = .68). In participants with baseline advanced adenomas, adenoma recurrence was reduced by 18% with selenium (RR = 0.82, 95% CI = 0.71 to 0.96, P = .01). In participants receiving selenium, the hazard ratio for new-onset T2D was 1.25 (95% CI = 0.74 to 2.11, P = .41), with a statistically significantly increased risk of selenium-associated T2D among older participants (RR = 2.21; 95% CI = 1.04 to 4.67, P = .03). Overall, selenium did not prevent colorectal adenomas and showed only modest benefit in patients with baseline advanced adenomas. With limited benefit and similar increases in T2D to other trials, selenium is not recommended for preventing colorectal adenomas in selenium-replete individuals.